Impact on clinical practice of a non-invasive gene expression melanoma rule-out test: 12-month follow-up of negative test results and utility data from a large US registry study

397 Background: An important step for a novel test is assessing its clinical utility and real-world effect on diagnosis and patient management. This report describes completed results of a cohort of physicians who have ordered a gene expression profile assay for identification of tumor tissue of origin (Pathwork Tissue of Origin Test) for patients with difficult-to-diagnose primary cancers and their subsequent treatment and survival. Methods: The IRB-approved registry collected data from participating physicians who have ordered the Tissue of Origin test. A detailed interview was conducted using both a web-based questionnaire and a confirmatory telephone interview with the physicians. Chart survey included collection of data on patient demographics, diagnostic procedures including imaging and immunohistochemistry as well as therapy. The physicians were queried regarding their working diagnoses and treatment recommendations prior to and after Tissue of Origin Test result availability. Date of death was also obtained with a minimum of one year follow-up from date of biopsy. Results: One hundred seven patients (61 women) have been studied and 65 participating physicians have completed the interview. Results indicate that most patients underwent extensive evaluation (≥ 10 IHC) prior to gene expression analysis. After receiving test results, physicians changed the primary site diagnosis for 53 patients (50%, CI [43,58%]; p<.001) and changed the treatment management for 72 patients (65%, CI [58%,73%]; p<.0001). At last follow-up, 69 patients had died with a median survival of 426 days. More than 30% of patients were alive at 1000 days. Conclusions: This registry study confirms that in patients with difficult-to-diagnose primary cancers, extensive baseline diagnostics are common and less than half of the patients have an established working diagnosis. Results indicate that the Tissue of Origin Test led to a change in working diagnosis and changed treatment recommendations in over half the patients. Survival outcomes compare favorably to historical controls in treatment trials where median survival is generally less than one year.

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Ectopic Pregnancies and Reproductive Capacity After Chlamydia trachomatis Positive and Negative Test Results: A Historical Follow-Up Study

Sexually Transmitted Diseases ◽

10.1097/01.olq.0000154512.86651.07 ◽

2005 ◽

Vol 32 (6) ◽

pp. 377-381 ◽

Cited By ~ 27

Author(s):

Berit Andersen ◽

Lars ??stergaard ◽

Erzsebet Puho ◽

Mette Vinther Skriver ◽

Henrik C. Sch??nheyder

Keyword(s):

Chlamydia Trachomatis ◽

Reproductive Capacity ◽

Test Results ◽

Negative Test ◽

Follow Up Study ◽

Ectopic Pregnancies

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Real-world experience and clinical utility of a non-invasive gene expression rule-out test for melanoma and additional validation against high risk driver mutations in BRAF, NRAS and the TERT promoter

SKIN The Journal of Cutaneous Medicine ◽

10.25251/skin.2.supp.69 ◽

2018 ◽

Vol 2 ◽

pp. S69

Author(s):

Laura Ferris ◽

Burkhard Jansen ◽

Zuxu Yao ◽

Jim Rock ◽

Maral Skelsey ◽

...

Keyword(s):

Gene Expression ◽

High Risk ◽

Real World ◽

Clinical Utility ◽

Driver Mutations ◽

Non Invasive ◽

Tert Promoter ◽

Rule Out

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Bladder Cancer Diagnosis and Follow-Up: The Current Status and Possible Role of Extracellular Vesicles

International Journal of Molecular Sciences ◽

10.3390/ijms20040821 ◽

2019 ◽

Vol 20 (4) ◽

pp. 821 ◽

Cited By ~ 15

Author(s):

Eline Oeyen ◽

Lucien Hoekx ◽

Stefan De Wachter ◽

Marcella Baldewijns ◽

Filip Ameye ◽

...

Keyword(s):

Bladder Cancer ◽

Clinical Practice ◽

Extracellular Vesicles ◽

Urine Cytology ◽

Diagnostic Methods ◽

Urinary Biomarkers ◽

Non Invasive ◽

Low Sensitivity

Diagnostic methods currently used for bladder cancer are cystoscopy and urine cytology. Cystoscopy is an invasive tool and has low sensitivity for carcinoma in situ. Urine cytology is non-invasive, is a low-cost method, and has a high specificity but low sensitivity for low-grade urothelial tumors. Despite the search for urinary biomarkers for the early and non-invasive detection of bladder cancer, no biomarkers are used at the present in daily clinical practice. Extracellular vesicles (EVs) have been recently studied as a promising source of biomarkers because of their role in intercellular communication and tumor progression. In this review, we give an overview of Food and Drug Administration (FDA)-approved urine tests to detect bladder cancer and why their use is not widespread in clinical practice. We also include non-FDA approved urinary biomarkers in this review. We describe the role of EVs in bladder cancer and their possible role as biomarkers for the diagnosis and follow-up of bladder cancer patients. We review recently discovered EV-derived biomarkers for the diagnosis of bladder cancer.

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Age-Adjusted D-Dimer Cut-off Levels to Rule out Pulmonary Embolism: A Prospective Outcome Study

Blood ◽

10.1182/blood.v122.21.lba-4.lba-4 ◽

2013 ◽

Vol 122 (21) ◽

pp. LBA-4-LBA-4

Author(s):

Marc Righini ◽

Paul den Exter ◽

Josien van ES ◽

Franck Verschuren ◽

Alexandre Ghuisen ◽

...

Keyword(s):

Pulmonary Embolism ◽

Clinical Practice ◽

Emergency Room ◽

Pulmonary Angiography ◽

Outcome Study ◽

Clinical Probability ◽

Imaging Test ◽

D Dimer ◽

Rule Out

Abstract Introduction D-dimer testing allows to safely rule out pulmonary embolism (PE) without imaging test in approximately one third of outpatients. However, D-Dimer test is less useful as age increases because of a lower specificity. We recently derived an age-adjusted D-dimer cut-off value (age-adjusted cut-off = patient’s age x 10 in patients aged > 50 years, in μg/L), which allowed to significantly increase the proportion of patients in whom PE could be non-invasively excluded, without compromising safety. However, before being implemented in clinical practice, the safety of the age-adjusted cut-off should be verified in a management outcome study. Methods We designed a multicentre multinational prospective management outcome study. All consecutive outpatients seen in the emergency room of 22 centres in 4 countries with clinically suspected PE were assessed by a sequential diagnostic strategy based on the assessment of clinical probability, D-dimer measurement and computed tomography pulmonary angiography (CTPA). Patients with a D-dimer value between the usual threshold of 500 μg/L and their age-adjusted cut-off did not undergo CTPA and were left untreated and formally followed for a three-month period. Results Between January 1, 2010 and February 28, 2013, we included 3,377 patients. Mean age was 62 years, and 57% were females. Overall, the proportion of confirmed PE was 18%. Among the 2,927 patients with a non-high clinical probability, 832 (28.4%) had a D-Dimer < 500 μg/L, and 345 additional patients (11.8%) had a D-Dimer comprised between 500 μg/L and their age-adjusted cut-off. During the 3-month follow-up period, out of the 345 patients with a D-Dimer between 500 μg/L and their age-adjusted cut-off, 18 patients received anticoagulation for another indication than PE. Of the remaining 327 patients, 7 died, and 7 underwent testing for suspected venous thromboembolism (VTE), of which one was confirmed. Therefore, the failure rate of the age-adjusted cut-off was 1/327: 0.3%, (95% CI 0.1 to 1.7%). Overall, 789 patients were aged 75 years or more, of them 697 had a non-high clinical probability. The proportion of patients with D-Dimer < 500 μg/L was 50/697 (7.2%). Another 161 patients had a D-Dimer above 500 μg/L and under their age-adjusted cut-off. Therefore, the proportion of patients > 75 with a negative D-Dimer using the age-adjusted cut-off was 211/697 (30.3%), of them none had a confirmed VTE during follow-up: 0.0%, (95%CI: 0.0 to 1.9%). Conclusions Our study demonstrates that the age-adjusted D-Dimer cut-off may now be used in clinical practice in emergency room patients with suspected PE. Combined with clinical probability, it increases the number of patients in whom PE can be excluded without imaging test, and this is particularly true among elderly patients, with a four-fold increased yield of D-dimer. A D-Dimer above 500 μg/L but under the age-adjusted cut-off safely excludes the diagnosis of PE, with a 3-month risk of VTE in line with that observed in patients with a D-Dimer under 500 μg/L or after a negative pulmonary angiography, the gold-standard test for PE. Disclosures: No relevant conflicts of interest to declare.

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Non-invasive assessment of peritoneal membrane alterations

Bulletin de la Dialyse à Domicile ◽

10.25796/bdd.v3i4.55893 ◽

2020 ◽

Vol 3 (3) ◽

pp. 119-126

Author(s):

Raymond Krediet ◽

Alena Parikova

Keyword(s):

Gene Expression ◽

Peritoneal Dialysis ◽

Ca 125 ◽

Non Invasive ◽

Morphological Studies ◽

Peritoneal Transport ◽

Appearance Rate ◽

Its Gene ◽

Pai 1

The peritoneal dialysis membrane is subject to remodelling in the course of peritoneal dialysis. In the absence of longitudinal morphological studies, this process is mainly studied indirectly by the investigation of changes in peritoneal transport. Non-invasive assessment of the peritoneum is also possible by assessment of substances that originate from peritoneal tissues and can be determined either as their gene expression in peritoneal effluent cells and/or as proteins in peritoneal effluent. Three of these biomarkers will be discussed, because longitudinal data are available. Cancer antigen 125 (CA 125) is present on the mesothelium,while its gene (MUC 16) is expressed in peritoneal effluent cells and is related to dialysate CA 125 protein. The constitutive production and the small intra-individual variability of 15% indicate its usefulness as a follow-up marker of mesothelial cell mass. Dialysate appearance rate is higher on biocompatible than on conventional solutions, but both decrease during long-term follow-up. Interleukin-6 (Il-6) is present in peritoneal effluent due to both transport from the circulation and local intraperitoneal production. Its appearance rate is unrelated to its gene expression in peritoneal cells. The intra-individual variation of effluent Il-6 averages 28%, hampering the interpretation of cross-sectional values. The relationships between effluent Il-6 and peritoneal transport have been interpreted as microinflammation, but are difficult to interprete due to mathematical coupling. Plasminogen activator inhibitor-1 (PAI-1) is encoded by the SERPINE 1 gene. A relationship is present between effluent concentration and gene expression. PAI-1 production is stimulated by glucose. PAI-1 appearance rate increases with PD duration. The sensitivity of effluent PAI-1 for the diagnosis of encapsulating peritoneal sclerosis was 100% one year prior to the diagnosis and the specificity 56%. It can be concluded that the discussed biomarkers are useful extensions to transport in assessment of the peritoneum during dialysis.

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