Predictive Testing Research Articles

Lipid-associated GWAS loci as important markers of the risk, severity, and clinical course of peripheral artery disease

ABSTRACT Background This study investigated the relationship between lipid-associated loci identified through genome-wide association studies (GWAS) and the risk of peripheral artery disease (PAD), its severity, as well as clinical and laboratory features. Research design and methods A study included 1263 unrelated Russian subjects, consisting of 620 patients diagnosed with PAD and 643 healthy controls. Thirteen single nucleotide polymorphisms (SNP) were genotyped using the MassArray-4 system. Results Polymorphisms rs1689800, rs55730499 and rs881844 were found to be associated with an increased risk of PAD, whereas SNPs rs1883025, rs3136441, rs3764261 and rs6065906 showed protective effects against disease (Pperm ≤ 0.05). SNPs rs1689800, rs217406, rs1883025, and rs3136441 exhibited combined effects with cigarette smoking on the PAD risk (Pperm ≤ 0.05). Polymorphisms rs55730499 (beta = 0.124, Pperm = 0.04), rs9987289 (beta = 0.558, Pperm = 0.03), and rs881844 beta = −0.171, Pperm = 0.03) correlated with the ankle-brachial index. Multiple associations have been found between the SNPs and clinically significant characteristics, including disease severity, risk of gangrene, early disease onset, plasma procoagulant and atherogenic lipid changes (Pperm ≤ 0.05). Conclusions We identified novel genetic markers associated with PAD susceptibility and disease-related clinical and laboratory features. The identified biomarkers enhance the potential for predictive genetic testing related to the risk and progression of PAD, facilitating the integration of molecular diagnostics into clinical decision-making processes.

Registering Theory-Based Predictions in Political Science

ABSTRACT How can political scientists rigorously evaluate the predictive power of theories? Many peer-reviewed political science articles include predictions about future outcomes, and scholars make predictions on social media and other public forums. The prevalence of predictions suggests that scholars recognize the utility of leveraging theories for this purpose; however, the predictions often are not made in a manner that allows for rigorously evaluating their accuracy. Building on the increasing popularity of study preregistration in the social sciences, this article proposes “prediction registration” as a means for scholars to publish falsifiable, systematic, and verifiable theory-based predictions. Increasing the rigor of predictive theory testing can advance often-circular debates about accuracy and presents a “win-win” for scholars who aim to test the predictive power of theories. With a more rigorous approach, correct predictions would better demonstrate a theory’s ability to forecast outcomes, and missed predictions would reveal information that can be used to calibrate the theory.

Earthquake Predictability and Forecast Evaluation Using Likelihood-Based Marginal and Conditional Scores

Abstract Earthquake probability forecasts are typically based on simulations of seismicity generated by statistical (point process) models or direct calculation when feasible. To systematically assess various aspects of such forecasts, the Collaborative Studies on Earthquake Predictability testing center has utilized N- (number), M- (magnitude), S- (space), conditional likelihood-, and T- (Student’s t) tests to evaluate earthquake forecasts in a gridded space–time range. This article demonstrates the correct use of point process likelihood to evaluate forecast performance covering marginal and conditional scores, such as numbers, occurrence times, locations, magnitudes, and correlations among space–time–magnitude cells. The results suggest that for models that only rely on the internal history but not on external observation to do simulation, such as the epidemic-type aftershock sequence model, test and scoring can be rigorously implemented via the likelihood function. Specifically, gridding the space domain unnecessarily complicates testing, and evaluating spatial forecasting directly via marginal likelihood might be more promising.

Psychosocial impact on individuals who received negative test results from predictive testing for Huntington's disease: Anexploratory qualitative study.

Huntington's disease (HD) is a neurodegenerative disease with autosomal dominant inheritance, and no radical cure for HD has been established. Qualitative studies are necessary to investigate the psychological state of individuals who underwent predictive testing for HD, because the psychosocial impact on noncarriers remains unclarified in Japan. Herein, we elucidated the psychosocial impact on the noncarriers for HD and the role of genetic counseling for predictive testing and follow-up after testing by examining their experiences with predictive testing. We conducted semi-structured interviews with eight individuals participating in this study. Interview data were transcribed verbatim and evaluated according to thematic analysis. As a result, 4 themes were generated from 21 categories of 46 codes: (1) Diversity of perceptions concerning the test results, (2) Views on life as a noncarrier, (3) Changes in feelings toward and relationships with family members, and (4) Sharing information within the family. After receiving the negative results, the noncarriers felt not only relief but also surprise, doubt, relief from tension, and regret. It was shown that noncarriers felt survivor's guilt toward many unspecified individuals, which was not only a sense of guilt but also a sense of mission or responsibility. Additionally, they conducted altruistic behavior as members of their family and society, that may be related to the Japanese collectivism. Some participants were concerned about sharing information with their siblings. Noncarriers for HD can experience complex psychological states, and Japanese people who prefer high-context communication may find it difficult to express their feelings and thoughts. It is important to understand their true feelings before and after the predictive genetic testing, reconsider the impact of being a noncarrier and whether it is a burden for them from both subjective and objective perspectives, and conduct long-term follow-up as needed.

The implementation and outcome of a breast cancer genetic counselling service at Potchefstroom Hospital: a model for outreach

Aim Breast cancer is the most prevalent cancer in South African females, making up 27.1% of all histologically diagnosed cancers in 2020. Although genetic technology and awareness of genetic counselling have improved, genetic counselling services in South Africa remain largely inaccessible. Clinical genetic services are only formally available in four South African provinces and few outreach programmes exist for small towns and cities. Until 2019, genetic counselling services were unavailable in the North West province; however, since then, genetic counsellors from the National Health Laboratory Service and the University of the Witwatersrand have provided genetic counselling services to patients at the Breast Clinic at Potchefstroom Hospital regularly each year. Method The aim of this pilot study was to perform a retrospective file review and report on the implementation and outcomes of the genetic counselling service at the Breast Clinic at Potchefstroom Hospital, from its inception in 2019, until November 2022. Fifty-two patients attended a genetic counselling consultation during that period. Results The majority of patients (83.7%) were diagnosed with an invasive ductal carcinoma, and 57.7% of the patients had a family history of cancer. A total of 62.8% of patients had a histologic grade 3 tumour. A total of 25.5% (12/47) of patients tested positive for a pathogenic variant in BRCA1 or BRCA2. A total of 45 at-risk first-degree relatives were identified who could benefit from predictive testing. Conclusions This study highlights the benefit of offering clinical genetics services through outreach clinics. Being able to offer this service is not only beneficial for the management of the affected individuals, but also for their at-risk relatives. The initiative serves as a positive example of how limited resources can be extended to benefit patients.

Genetic counseling development and milestone in Oman

Genetic counseling as an emerging profession has seen an expansion around the world. In the Sultanate of Oman, the profession has developed with the establishment of clinical and biochemical genetic services in 2010 and genetic counseling services in 2011. Currently, three main genetic counseling teams serve the country through qualified genetic counselors who completed internationally-recognized MSc program. The genetic counselors are working in governmental clinical genetic units and play vital roles in enhancing the quality of genetic services dealing with pediatric and adult-onset disorders. The impact of the service is reflected in the escalated demand for preventative measures such as alternative reproductive options, premarital genetic counseling and testing as well as predictive counseling and testing. Despite the limited resources and absence of a licensing body, the genetic counseling profession in Oman is progressing. This special report describes the development of genetic counseling in Oman and the milestones reached. It details the areas of service, scope of practice, and the unique social and cultural nuances inherent to genetic counseling in Oman.

Comparison of Risk Stratification by CanAssist Breast Test Performed on Core Needle Biopsies Versus Surgical Specimens in Hormone Receptor-Positive, Her2-Negative Early Breast Cancer.

Introduction Core needle biopsies (CNB) are being increasingly utilized for biomarker, prognostic, and predictive testing in breast cancer (BC).CanAssist Breast (CAB) is a prognostic test performed to assess the 'risk of breast cancer recurrence' in early-stage hormone receptor-positive, Her2-negative BC patients. CAB segregates tumors as 'low risk' or 'high risk' for distant recurrence.Risk assessment done by CAB aids in planning and making adjuvant chemotherapy or hormone therapy decisions.CAB is typically performed on surgical specimens (SS).However, performing it on CNB does offer additional insights into tumor biology leading to different strategies for treatment planning; hence, we aimed to compare the risk stratification performance of CAB using CNB versus SS. Method We analyzed 103 paired formalin-fixed paraffin-embedded CNB and SS samples from hormone receptor-positive, Her2-negative early BC tissue samples submitted for performing CAB at OncoStem Diagnostics between November 2021 and September 2023. Concordance on 'risk categories' of CAB performed on CNB versus SS was reported using overall percentage agreement and Pearson correlation coefficient. Results We found excellent overall concordance of 92.2% for CAB risk stratification between paired CNB and SS tumor samples with a strong Pearson correlation coefficient of r= 0.8351 (p< 0.0001) when either SS or CNB was used as the gold standard.In prognostic testing patients with a 'low risk' of recurrence may avoid chemotherapy and hence it is crucial to assess the accuracy of CAB in the low-risk category. Additionally, in a real-world scenario, it is more likely that CAB will be performed on CNB first. Conclusion CAB when performed on CNB samples showed high concordance with SS thus demonstrating that CNB was a suitable sample for the CanAssist Breast test.The accuracy in the low-risk category is 97.5%, which ensures that physicians can reliably use prognostic information by testing CNB to guide adjuvant therapy decisions.

Non-perpetual eternal inflation and the emergent de Sitter Swampland conjecture

We introduce a novel correlation, ns\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$n_{\ ext {s}}$$\\end{document} - ΔN\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\Delta N$$\\end{document}, connecting CMB parameters to the required total e-folds for eternal inflation. This correlation provides a robust tool for evaluating eternal (string) inflation models using CMB data and explores the impact of quantum fluctuations on non-attractor phases. By generalizing eternal inflation criteria, our parameterization simplifies rigorous testing of predictions and reveals a link between refined de Sitter conjecture parameters and the eternal nature of the cosmic landscape. This points to a general tendency towards eternal behavior in low-energy effective field theories within the landscape, opening the possibility for our cosmic stage to potentially embrace a ’multiverse’ scenario.

Kinematic analysis of multiple Compton scattering in quantum-entangled two-photon systems

The Stokes–Mueller method is used to analyze the scattering of entangled photon pairs in a two-photon system. This study examines the scenario where one of the photons, part of a pair of maximally entangled annihilation photons, undergoes intermediate Compton scattering before both photons are detected using Compton polarimeters. The method also accounts for potential quantum-decoherence effects resulting from Compton scattering. The analysis investigates the scattering behavior in both parallel and perpendicular planes, identifying variations in the modulation factor that affect azimuthal correlations. These variations include increases, decreases, sign changes, or disappearances at certain intermediate scattering angles. This work aims to provide theoretical results that support the testing and verification of predictions made by quantum field theory.

Parent attitudes towards predictive testing for autism in the first year of life

BackgroundEmerging biomarker technologies (e.g., MRI, EEG, digital phenotyping, eye-tracking) have potential to move the identification of autism into the first year of life. We investigated the perspectives of parents about the anticipated utility and impact of predicting later autism diagnosis from a biomarker-based test in infancy.MethodsParents of infants were interviewed to ascertain receptiveness and perspectives on early (6-12 months) prediction of autism using emerging biomarker technologies. One group had experience parenting an older autistic child (n=30), and the other had no prior autism parenting experience (n=25). Parent responses were analyzed using inductive qualitative coding methods.ResultsAlmost all parents in both groups were interested in predictive testing for autism, with some stating they would seek testing only if concerned about their infant’s development. The primary anticipated advantage of testing was to enable access to earlier intervention. Parents also described the anticipated emotions they would feel in response to test results, actions they might take upon learning their infant was likely to develop autism, attitudes towards predicting a child’s future support needs, and the potential impacts of inaccurate prediction.ConclusionIn qualitative interviews, parents of infants with and without prior autism experience shared their anticipated motivations and concerns about predictive testing for autism in the first year of life. The primary reported motivators for testing—to have more time to prepare and intervene early—could be constrained by familial resources and service availability. Implications for ethical communication of results, equitable early intervention, and future research are discussed.

Developing a Paired Whole Genome Sequencing Service for Children With Cancer

BackgroundThe uniqueness of paired (tumor and germline) whole genome sequencing (PWGS) in cancer diagnosis and management lies in not just its ability to uncover oncogenic drivers and potential treatment targets but also on the identification of underlying cancer predisposition syndromes, which has significant implications for the patient and their family. AimsThis is a descriptive article highlighting the processes taken by our team to incorporate PWGS into routine National Health Service (NHS) clinical care for children with cancer. The main aim of this article is to share our experience with other centers that may wish to set up similar services and set the stage for future quantitative/qualitative research. MethodsThis article is further supported by an audit focusing on children in whom an underlying cancer predisposition was confirmed. ResultsThe audit highlights the success of the program to date, with 100% of families identified as being at risk of a cancer predisposition syndrome being offered referral to clinical genetics and 100% of at-risk first-degree relatives being offered predictive counseling and testing. Areas requiring improvement included discussion of reproductive options as only six out of nine families (67%) had a documented discussion. ConclusionsIncorporation of the audit recommendations will improve our service, and sharing of our experience will hopefully encourage more pediatric oncology services to introduce PWGS into routine clinical care and reduce inequity of access. Further work is required to assess the long-term cancer risk reduction and establish the psychosocial impact of PWGS for the child and family.

Using polygenic risk modification to improve breast cancer prevention: study protocol for the PRiMo multicentre randomised controlled trial

IntroductionEstablished personal and familial risk factors contribute collectively to a woman’s risk of breast or ovarian cancer. Existing clinical services offer genetic testing for pathogenic variants in high-risk genes to...

Fluid Biomarkers in Individuals at Risk for Genetic Prion Disease up to Disease Conversion.

To longitudinally characterize disease-relevant CSF and plasma biomarkers in individuals at risk for genetic prion disease up to disease conversion. This single-center longitudinal cohort study has followed known carriers of PRNP pathogenic variants at risk for prion disease, individuals with a close relative who died of genetic prion disease but who have not undergone predictive genetic testing, and controls. All participants were asymptomatic at first visit and returned roughly annually. We determined PRNP genotypes, measured NfL and GFAP in plasma, and RT-QuIC, total PrP, NfL, T-tau, and beta-synuclein in CSF. Among 41 carriers and 21 controls enrolled, 28 (68%) and 15 (71%) were female, and mean ages were 47.5 and 46.1. At baseline, all individuals were asymptomatic. We observed RT-QuIC seeding activity in the CSF of 3 asymptomatic E200K carriers who subsequently converted to symptomatic and died of prion disease. 1 P102L carrier remained RT-QuIC negative through symptom conversion. No other individuals developed symptoms. The prodromal window from detection of RT-QuIC positivity to disease onset was 1 year long in an E200K individual homozygous (V/V) at PRNP codon 129 and 2.5 and 3.1 years in 2 codon 129 heterozygotes (M/V). Changes in neurodegenerative and neuroinflammatory markers were variably observed prior to onset, with increases observed for plasma NfL in 4/4 converters, and plasma GFAP, CSF NfL, CSF T-tau, and CSF beta-synuclein each in 2/4 converters, although values relative to age and fold changes relative to individual baseline were not remarkable for any of these markers. CSF PrP was longitudinally stable with mean coefficient of variation 9.0% across all individuals over up to 6 years, including data from converting individuals at RT-QuIC-positive timepoints. CSF prion seeding activity may represent the earliest detectable prodromal sign in E200K carriers. Neuronal damage and neuroinflammation markers show limited sensitivity in the prodromal phase. CSF PrP levels remain stable even in the presence of RT-QuIC seeding activity. ClinicalTrials.gov NCT05124392 posted 2017-12-01, updated 2023-01-27.

Unlocking the potential of microfold cells for enhanced permeation of nanocarriers in oral drug delivery

The therapeutic effects of orally administered nanocarriers depend on their ability to effectively permeate the intestinal mucosa, which is one of the major challenges in oral drug delivery. Microfold cells are specialized enterocytes in the intestinal epithelium known for their high transcytosis abilities. This study aimed to compare and evaluate two targeting approaches using surface modifications of polymer-based nanocarriers, whereas one generally addresses enterocytes, and one is directed explicitly to microfold cells via targeting the sialyl LewisA motif on their surface. We characterized the resulting carriers in terms of size and charge, supplemented by scanning electron microscopy to confirm their structural properties. For predictive biological testing and to assess the intended targeting effect, we implemented two human intestinal in vitro models containing microfold-like cells. Both models were thoroughly characterized prior to permeation studies with the different nanocarriers. Our results demonstrated improved transport for both targeted formulations compared to undecorated carriers in the in vitro models. Notably, there was an enhanced uptake in the presence of microfold-like cells, particularly for the nanocarriers directed by the anti-sialyl LewisA antibody. These findings highlight the potential of microfold cell targeting to improve oral administration of drugs and emphasize the importance of using suitable and well-characterized in vitro models for testing novel drug delivery strategies.

Accelerated degradation testing impacts the degradation processes in 3D printed amorphous PLLA.

Additive manufacturing and electrospinning are widely used to create degradable biomedical components. This work presents important new data showing that the temperature used in accelerated tests has a significant impact on the degradation process in amorphous 3D printed poly-l-lactic acid (PLLA) fibres. Samples (c. 100 m diameter) were degraded in a fluid environment at C, C and C over a period of 6months. Our findings suggest that across all three fluid temperatures, the fibres underwent bulk homogeneous degradation. A three-stage degradation process was identified by measuring changes in fluid pH, PLLA fibre mass, molecular weight and polydispersity index. At C, the fibres remained amorphous but, at elevated temperatures, the PLLA crystallised. A short-term hydration study revealed a reduction in glass transition (Tg), allowing the fibres to crystallise, even at temperatures below the dry Tg. The findings suggest that degradation testing of amorphous PLLA fibres at elevated temperatures changes the degradation pathway which, in turn, affects the sample crystallinity and microstructure. The implication is that, although higher temperatures might be suitable for testing bulk material, predictive testing of the degradation of amorphous PLLA fibres (such as those produced via 3D printing or electrospinning) should be conducted at C.

Biomarkers for Early Disease Detection: Advancements in Predictive Medicine and Diagnostic Testing

Biomarkers have emerged as invaluable tools in predictive medicine and diagnostic testing, revolutionizing our approach to early disease detection. This paper examines recent advancements in biomarker research and their implications for identifying diseases at their earliest stages. Through genomic, proteomic, metabolic, and microbiome-based biomarkers, coupled with the power of liquid biopsies and artificial intelligence, clinicians can now detect diseases with unprecedented accuracy and timeliness. We explore the role of genomic biomarkers, such as BRCA1/BRCA2 mutations, proteomic markers like PSA for prostate cancer, and metabolic indicators such as blood glucose levels for diabetes. Liquid biopsies offer non-invasive methods for detecting early-stage cancers and monitoring treatment response. Microbiome-based biomarkers illuminate the intricate relationship between microbial communities and disease states.

Testing the Adaptive Market Hypothesis and Time-Varying Efficiency in the Indian Equity Market

The study examines the adaptive market hypothesis (AMH) as an evolutionary principle of the alternative efficient market hypothesis in the Indian stock market (Sensex and Nifty50) on the daily return from April 2014 to May 2020. Based on AMH, investors behave, learn, and adapt to market conditions. This distinction of dynamic market conditions is divided into bull and bear market classifications. We apply three variations of the variance ratio test and the returns have been whitened using the Autoregressive model with generalized autoregressive conditional heteroskedasticity (AR-GARCH) approach to examine the nonlinear predictability test. Further, we evaluate a fixed-length subsample window framework to detect the time-varying predictability and examine whether market conditions affect stock return predictability and market condition. The study confirms inefficient market behaviour during crises, fear, panic, macroeconomic events and each market adapts differently to certain market conditions. Furthermore, the return series exhibits significant periods of efficiency and inefficiency consistent with the adaptive market hypothesis. The evidence of our findings sheds light on efficient market behaviour in dynamic market conditions and market environments for researchers, investors in investment strategies and policy intervention in risk containment measures and control market manipulation.

Interaction networks within disease-associated GαS variants characterized by an integrative biophysical approach

Activation of G proteins through nucleotide exchange initiates intracellular signaling cascades essential for life processes. Under normal conditions, nucleotide exchange is regulated by the formation of G protein–G protein-coupled receptor (GPCR) complexes. Single point mutations in the Gα subunit of G proteins bypass this interaction, leading to loss-of-function or constitutive gain-of-function, which is closely linked with the onset of multiple diseases. Despite the recognized significance of Gα mutations in disease pathology, structural information for most variants is lacking, potentially due to inherent protein dynamics that pose challenges for crystallography. To address this, we leveraged an integrative spectroscopic and computational approach to structurally characterize seven of the most frequently observed clinically-relevant mutations in the stimulatory Gα subunit, GαS. A previously proposed allosteric model of Gα activation linked structural changes in the nucleotide binding pocket with functionally important changes in interactions between switch regions. We investigated this allosteric connection in GαS by integrating data from variable temperature CD spectroscopy, which measured changes in global protein structure and stability, and molecular dynamics (MD) simulations, which observed changes in interaction networks between GαS switch regions. Further, saturation-transfer difference NMR (STD–NMR) spectroscopy was applied to observe changes in nucleotide interactions with residues within the nucleotide binding site. These data have enabled testing of predictions regarding how mutations in GαS result in loss or gain of function and evaluation of proposed structural mechanisms. The integration of experimental and computational data allowed us to propose a more nuanced classification of mechanisms underlying GαS gain-of-function and loss-of-function mutations.

Lynch syndrome

Patients with Lynch syndrome, one of the most common hereditary tumor predisposition syndromes, harbor an increased risk for abroad spectrum of especially gastrointestinal and gynecological tumors. Causative for the syndrome are variants in DNA mismatch repair genes, which are passed on to the offspring at a50% chance (autosomal dominant inheritance). The tumor tissue of these patients usually shows microsatellite instability, which is of increasing relevance regarding prognosis and therapeutic decisions. The detection of acausative genetic variant in apatient enables predictive testing of family members to provide relief to noncarriers and provide carriers with intensified risk-adapted surveillance. In addition, chemoprevention with aspirin (acetylsalicylic acid) has been proven useful for chemoprevention in studies. Therefore, the diagnosis of Lynch syndrome is important for patients and their relatives.

Multi-specimen comprehensive genomic profiling for diagnostic disambiguation in advanced and metastatic solid tumors.

e15166 Background: Predictive biomarker testing for therapy selection is the primary intended use of tissue-based comprehensive genomic profiling (CGP) in advanced and metastatic cancer patients. This study aimed to characterize oncologists’ use of multi-specimen CGP to elucidate diagnostic uncertainty in the course of usual care for advanced and metastatic cancer patients. Methods: To assess the nature and extent to which CGP is potentially used for diagnostic disambiguation, we retrospectively identified patients tested at a reference laboratory with CGP at least twice (Illumina TruSight Oncology 500 assay), and the first two serial CGP tests for each patient were selected for study inclusion. We then explored patient demographics, rare ( &lt; 20 cases per 100k individuals) vs common diagnoses, tested tissue characteristics, time between CGP orders, and differences in genomic variant profiles between test pairs to characterize potential diagnostic use cases. Results: In all, 337/15,717 (2.1%) of patients underwent multi-CGP (June 2021-December 2023). All CGP test pairs were performed using different tissue specimens from 2 separate surgical cases (80.7%) or 2 different blocks for the same surgical case (19.3%). Compared to single-CGP, patients with multi-CGP were younger on average (65 vs 68 years), more often female (54.6% vs 50.6%), and had a greater proportion of lung (45.7% v 39.8%), breast (10.7% vs 6.7%), and unknown primary (7.1% vs 5.2%) tumors. CGP test pairs were grouped for comparison by test order diagnoses submitted by oncologists as: (Group 1) 2 different primary tumors (16%); (Group 2) same primary tumor, different histologic subtypes (19%), or; (Group 3) same primary tumor, same histologic subtype (65%). In Group 1, multi-CGP was performed more frequently for patients with a rare diagnosis for at least 1 test compared to Groups 2 and 3 (81.5% vs 43.8% or 19.6%, p &lt; 0.001), especially for cancers of unknown primary origin (31.5% vs 7.8% and 0.9%, p &lt; 0.001). In Groups 1 and 2, testing for both a primary and a metastatic site was twice as common compared to Group 3 (43% and 41% vs 22%, p = 0.017). In Group 3, 80% of patients were represented by common tumor types, and were most often tested &gt; 30 days apart (64.4%). The mean percent overlap in detected genomic variants was lowest for patients in Groups 1 and 2 where patients had 2 different primary diagnoses or 2 different histologies, and highest in Group 3, where patients had the same primary diagnosis and histology for both tests, (41.5%, 54.5%, 60%, p = 0.008). Conclusions: In practice, most multi-CGP testing is ordered serially for a subset of advanced cancer patients with common tumor types. Use of simultaneous multi-CGP for diagnostic decision-making appears to be limited to a fraction of patients representing more rare tumors with distinct diagnostic conundrums, warranting further exploration of clinical utility.