scholarly journals Causes behind error rates for predictive biomarker testing: the utility of sending post-EQA surveys

2020 ◽  
Author(s):  
Cleo Keppens ◽  
Ed Schuuring ◽  
Elisabeth M. C. Dequeker
Keyword(s):  
Colorectal Cancer ◽  
Test Performance ◽  
Predictive Biomarker ◽  
Recent Change ◽  
Error Rates ◽  
Test Methodology ◽  
Interpretation Errors ◽  
Biomarker Testing ◽  
Analysis Error ◽  
Eqa Schemes

AbstractExternal quality assessment (EQA) schemes assess the performance of predictive biomarker testing in lung and colorectal cancer and have previously demonstrated variable error rates. No information is currently available on the underlying causes of incorrect EQA results in the laboratories. Participants in EQA schemes by the European Society of Pathology between 2014 and 2018 for lung and colorectal cancer were contacted to complete a survey if they had at least one analysis error or test failure in the provided cases. Of the 791 surveys that were sent, 325 were completed including data from 185 unique laboratories on 514 incorrectly analyzed or failed cases. For the digital cases and immunohistochemistry, the majority of errors were interpretation-related. For fluorescence in situ hybridization, problems with the EQA materials were reported frequently. For variant analysis, the causes were mainly methodological for lung cancer but variable for colorectal cancer. Post-analytical (clerical and interpretation) errors were more likely detected after release of the EQA results compared to pre-analytical and analytical issues. Accredited laboratories encountered fewer reagent problems and more often responded to the survey. A recent change in test methodology resulted in method-related problems. Testing more samples annually introduced personnel errors and lead to a lower performance in future schemes. Participation to quality improvement projects is important to reduce deviating test results in laboratories, as the different error causes differently affect the test performance. EQA providers could benefit from requesting root cause analyses behind errors to offer even more tailored feedback, subschemes, and cases.

scholarly journals Immune Checkpoint Inhibitors in Urothelial Carcinoma: Recommendations for Practical Approaches to PD-L1 and Other Potential Predictive Biomarker Testing

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1424
Author(s):  
Antonio Lopez-Beltran ◽  
Fernando López-Rios ◽  
Rodolfo Montironi ◽  
Sophie Wildsmith ◽  
Markus Eckstein
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Best Practice ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarker ◽  
High Quality ◽  
The Status ◽  
Biomarker Testing ◽  
Novel Biomarkers ◽  
Scoring Algorithms

Immuno-oncology (IO) agents (anti–programmed cell death 1 (PD-1) and anti–programmed cell death-ligand 1 (PD-L1)) are approved as first- and second-line treatments for metastatic UC. PD-L1 expression levels in UC tumors help clinicians determine which patients are more likely to respond to IO therapies. Assays for approved IO agents use different antibodies, immunohistochemical protocols, cutoffs (defining “high” vs. “low” PD-L1 expression), and scoring algorithms. The robust control of pre-analytical and analytical standards is needed to obtain high-quality PD-L1 results. To better understand the status and perspectives of biomarker-guided patient selection for anti–PD-1 and anti–PD-L1 agents in UC, three workshops were held from December 2018 to December 2019 in Italy, Malaysia, and Spain. The primary goal was to develop recommendations for best practice approaches to PD-L1 testing in UC. Recommendations pertaining to the interpretation and reporting of the results of PD-L1 assays from experienced pathologists and oncologists from around the globe are included. A test request form for pathology laboratories was developed as a critical first step for oncologists/urologists to encourage communication between clinicians and pathologists, ensuring fast and high-quality test results. In this era of personalized medicine, we briefly discuss novel biomarkers being evaluated for IO agents in UC.

scholarly journals EphA2 and EGFR: Friends in Life, Partners in Crime. Can EphA2 Be a Predictive Biomarker of Response to Anti-EGFR Agents?

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 700
Author(s):  
Mario Cioce ◽  
Vito Michele Fazio
Keyword(s):  
Colorectal Cancer ◽  
Solid Tumors ◽  
Receptor Tyrosine Kinase ◽  
Predictive Biomarker ◽  
Eph Receptors ◽  
Oncogenic Signaling ◽  
Induced Stress ◽  
Molecular Determinants ◽  
Signaling Axis ◽  
Context Specific

The Eph receptors represent the largest group among Receptor Tyrosine kinase (RTK) families. The Eph/ephrin signaling axis plays center stage during development, and the deep perturbation of signaling consequent to its dysregulation in cancer reveals the multiplicity and complexity underlying its function. In the last decades, they have emerged as key players in solid tumors, including colorectal cancer (CRC); however, what causes EphA2 to switch between tumor-suppressive and tumor-promoting function is still an active theater of investigation. This review summarizes the recent advances in understanding EphA2 function in cancer, with detail on the molecular determinants of the oncogene-tumor suppressor switch function of EphA2. We describe tumor context-specific examples of EphA2 signaling and the emerging role EphA2 plays in supporting cancer—stem—cell-like populations and overcoming therapy-induced stress. In such a frame, we detail the interaction of the EphA2 and EGFR pathway in solid tumors, including colorectal cancer. We discuss the contribution of the EphA2 oncogenic signaling to the resistance to EGFR blocking agents, including cetuximab and TKIs.

scholarly journals Circulating tumor cell-related transcripts in blood as prognostic biomarkers of early recurrence after liver resection for colorectal metastases

2019 ◽  
Vol 34 (3) ◽  
pp. 269-275
Author(s):  
Felice Giuliante ◽  
Elena Panettieri ◽  
Francesco Ardito ◽  
Agostino De Rose ◽  
Krizia Pocino ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Resection ◽  
Tumor Cell ◽  
Carcinoembryonic Antigen ◽  
Growth Factor Receptor ◽  
Predictive Biomarker ◽  
Circulating Tumor Cell ◽  
Early Recurrence ◽  
Colorectal Metastases

Background: Several prognostic factors were proposed to improve early detection of recurrence after liver resection of metastases of colorectal cancer. Circulating tumor cell-related transcripts were evaluated in colorectal cancer patients with conflicting results. The aim of this study was to investigate usefulness of carcinoembryonic antigen CAM5, epidermal growth factor receptor, and ERCC1 transcripts in the bloodstream as predictive factors of recurrence in patients who underwent liver resection for metastases of colorectal cancer. Methods: Peripheral blood was collected from 29 patients at the time of the colorectal cancer liver metastasis resection, and from 25 normal controls. Follow-up draws (FUDs) were also performed at 30 days, and 3 and 12 months since surgery. On each sample, carcinoembryonic antigen CAM5, ERCC1, and GAPDH mRNAs were examined by quantitative reverse transcription (qRT). Results: Carcinoembryonic antigen transcript levels were linearly correlated to the number of spiked cells (qRT analytical limit = five cells). Among 29 patients (20 M/9 F; mean age 63 years (range 32–79), highly significant levels of carcinoembryonic antigen, if compared to the baseline, were detected in those relapsing after surgery ( P <0.05). The main differences were between the 1st- and 12th-month FUDs. Significantly higher levels of carcinoembryonic antigen were also detected in patients who died from disease progression during the follow-up (as evaluated at 30 days and 90 days FUDs). Conclusions: Blood carcinoembryonic antigen-mRNA absolute copy number overtime variation can represent a valid early predictor of relapse after liver resection in colorectal liver metastases patients. Prospective studies, in the context of large clinical trials, will provide further data to also qualify ERCC1 as a predictive biomarker for decisions on therapeutic strategies.

Guideline-recommended incorporation of biomarker testing results in metastatic colorectal cancer therapy

2020 ◽  
Vol 17 (3) ◽  
pp. 185-194
Author(s):  
Jared Freml ◽  
Thomas Delate ◽  
Jesus Hermosillo-Rodriguez
Keyword(s):  
Colorectal Cancer ◽  
Retrospective Study ◽  
Cancer Therapy ◽  
Metastatic Colorectal Cancer ◽  
Small Proportion ◽  
Biomarker Testing ◽  
Over Time

Aim: To describe pharmacogenomic tumor testing among patients with metastatic colorectal cancer. Methods: This was a retrospective study of patients with metastatic colorectal cancer diagnosed between 1 January 2014 and 30 June 2018. Patients were assessed for pharmacogenomic testing and appropriateness of chemotherapy use. Results: Overall, 112/167 (67.1%) patients had at least one of the three recommended pharmacogenomic tests and 41/167 (24.6%) had all tests. Twenty-four patients were treated with cetuximab with 8/167 (4.7%) identified as being treated with a RAS variant (n = 3) or incomplete testing (n = 5); thus, not in accordance with guidelines. Conclusion: Uptake of testing was variable but increased over time; however, a small proportion of patients received cetuximab with a variant or not all recommended tests being performed.

scholarly journals The Clinical Significance of MiR-148a as a Predictive Biomarker in Patients with Advanced Colorectal Cancer

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e46684 ◽  
Author(s):  
Masanobu Takahashi ◽  
Miriam Cuatrecasas ◽  
Francesc Balaguer ◽  
Keun Hur ◽  
Yuji Toiyama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Significance ◽  
Advanced Colorectal Cancer ◽  
Predictive Biomarker

Tumor bulk as a prognostic biomarker and predictor of benefit from anti-EGFR therapy in patients with metastatic colorectal cancer: Analysis of 476 patients from the ARCAD Clinical Trials Program.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 108-108
Author(s):  
Benjamin Adam Weinberg ◽  
Manel Rakez ◽  
Benoist Chibaudel ◽  
Tim Maughan ◽  
Richard Adams ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Primary Tumor ◽  
Lung Metastases ◽  
Performance Status ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Wild Type ◽  
Cox Models ◽  
Study Results

108 Background: Primary tumor sidedness has emerged as a prognostic and predictive biomarker for patients (pts) with metastatic colorectal cancer (mCRC). Tumor bulk has also been postulated to predict response to anti-EGFR therapy. We sought to evaluate the role of tumor bulk as a predictive biomarker to anti-EGFR therapy in pts with left- (LS) and right-sided (RS) mCRC. Methods: Data from 476 pts with mCRC enrolled across 2 first-line trials of anti-EGFR plus chemotherapy versus chemotherapy were pooled. Pts were included if there was available information on tumor sidedness and tumor bulk. All were KRAS wild-type and BRAF wild-type or unknown BRAF status. The right colon was defined as the cecum through the transverse colon, and the left colon as the splenic flexure through the rectum. Tumor bulk was the mean tumor size of target lesions at baseline, bulky defined as > 3.5 cm. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier and Cox models adjusting for performance status (PS), platelet count, primary tumor (PT) resection, number of metastatic sites, and stratified by study. Results: Pts with bulky tumors (211, 44%) had higher PS, white blood cell and platelet counts, higher CEA, fewer sites of metastatic disease, more liver than lung metastases, and fewer had PT resection. OS and PFS medians in months (mos) are presented in the table with 95% confidence intervals (95%CIs). Bulky tumors had inferior median OS compared with non-bulky (mOS, 17.9 vs. 21.3 mos, HRadj 1.33, 95% CI 1.05-1.69, P = 0.016) although median PFS was similar (mPFS, 8.6 vs. 8.7 mos, HRadj 1.15, 95% CI 0.92-1.42, P = 0.21). Conclusions: Tumor bulk is an independent prognostic factor for OS in KRAS wild-type and BRAF wild-type or unknown BRAF status pts. Pts with non-bulky RS tumors have survival outcomes similar to pts with bulky LS tumors. Although the mPFS for pts with RS tumors treated with anti-EGFR therapy was the lowest across subgroups, this finding was not statistically significant. Further research is warranted into whether pts with bulky RS tumors benefit from anti-EGFR therapy. Clinical trial information: NCT00182715, NCT00640081. [Table: see text]

A predictive biomarker for altered 5-fluorouracil pharmacokinetics following repeated administration in a rat model of colorectal cancer

2013 ◽  
pp. n/a-n/a
Author(s):  
Shinji Kobuchi ◽  
Shota Kuwano ◽  
Kazuki Imoto ◽  
Kae Okada ◽  
Asako Nishimura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rat Model ◽  
Predictive Biomarker ◽  
Repeated Administration

scholarly journals Tissue Microarray from Cell Block Material (cbTMA)—An Additional Shot for Cytology in the Predictive Pathology Era: The PD-L1 Experience

2022 ◽  
Vol 3 (1) ◽  
pp. 15-23
Author(s):  
Antonino Iaccarino ◽  
Gennaro Acanfora ◽  
Pasquale Pisapia ◽  
Umberto Malapelle ◽  
Claudio Bellevicine ◽  
...  
Keyword(s):  
Tissue Microarray ◽  
Large Scale ◽  
Metastatic Lymph Node ◽  
Predictive Biomarkers ◽  
Predictive Biomarker ◽  
Observer Agreement ◽  
Cell Block ◽  
Multicenter Studies ◽  
Ffpe Samples ◽  
Biomarker Testing

Generally, predictive biomarker tests are clinically validated on histological formalin-fixed, paraffin-embedded (FFPE) samples. In addition to FFPE samples, cytological samples have also emerged as a useful approach to detect predictive biomarkers. However, as of today, despite the promising results reported in the recent literature, their full implementation in routine clinical practice is still lagging owing to a lack of standardized preparatory protocols, challenging assessments of cyto-histological correlation, and variable inter-observer agreement. The aim of this report was to explore the possibility of implementing a large-scale validation of predictive biomarker testing on cytological material. To this aim, we evaluated the technical feasibility of PD-L1 assessment on a cell block (CB)-derived tissue microarray (cbTMA). Consecutive and unselected CBs prepared from metastatic lymph node fine-needle cytology (FNC) samples were retrospectively collected and used for TMA construction. PD-L1 immunohistochemistry (IHC) was carried out on cbTMA sections with the companion diagnostic kit SP263 assay. TMA contained 33 CB-derived cores. A total of 20 sections were hematoxylin and eosin (H&E) stained. Overall, 29 (88%) samples were visible at least in one H&E-stained slide. Four cases out of five sections stained with the SP263 assay (4/29, 13.8%) showed PD-L1 positivity in neoplastic and/or immune cells; remarkably, no unspecific background was observed. Although our study was based on a limited and non-selected series, our findings do provide proof of concept for the use of cbTMA in predictive biomarker testing on cytological material in large-scale post-clinical trial validation studies, multicenter studies, and quality control programs.

scholarly journals The effects of gamelike features and test location on cognitive test performance and participant enjoyment

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2184 ◽  
Author(s):  
Jim Lumsden ◽  
Andy Skinner ◽  
Andy T. Woods ◽  
Natalia S. Lawrence ◽  
Marcus Munafò
Keyword(s):  
Test Performance ◽  
Cognitive Task ◽  
Reaction Times ◽  
Error Rates ◽  
Cognitive Testing ◽  
Quality Data ◽  
Cognitive Test ◽  
Test Location ◽  
Gamelike Features ◽  
Time Accuracy

Computerised cognitive assessments are a vital tool in the behavioural sciences, but participants often view them as effortful and unengaging. One potential solution is to add gamelike elements to these tasks in order to make them more intrinsically enjoyable, and some researchers have posited that a more engaging task might produce higher quality data. This assumption, however, remains largely untested. We investigated the effects of gamelike features and test location on the data and enjoyment ratings from a simple cognitive task. We tested three gamified variants of the Go-No-Go task, delivered both in the laboratory and online. In the first version of the task participants were rewarded with points for performing optimally. The second version of the task was framed as a cowboy shootout. The third version was a standard Go-No-Go task, used as a control condition. We compared reaction time, accuracy and subjective measures of enjoyment and engagement between task variants and study location. We found points to be a highly suitable game mechanic for gamified cognitive testing because they did not disrupt the validity of the data collected but increased participant enjoyment. However, we found no evidence that gamelike features could increase engagement to the point where participant performance improved. We also found that while participants enjoyed the cowboy themed task, the difficulty of categorising the gamelike stimuli adversely affected participant performance, increasing No-Go error rates by 28% compared to the non-game control. Responses collected online vs. in the laboratory had slightly longer reaction times but were otherwise very similar, supporting other findings that online crowdsourcing is an acceptable method of data collection for this type of research.

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