Lien Tembuyser

External Quality Assessment Unravels Interlaboratory Differences in Quality of RAS Testing for Anti-EGFR Therapy in Colorectal Cancer

BACKGROUND Regulations for the selection of patients with metastatic colorectal cancer for anti-EGFR treatment changed at the end of 2013. The set of mutations to be tested extended from KRAS codons 12 and 13 to KRAS and NRAS exons 2, 3, and 4. A European external quality assessment scheme monitored the performance of laboratories and evaluated the implementation of the new regulations. MATERIALS AND METHODS The 131 participating laboratories received 10 samples of formalin-fixed paraffin-embedded material, including RAS (exon 2, 3, 4) and BRAF mutations. Mock clinical data were provided for three cases. Using their routine methods, laboratories determined the genotypes and submitted three written reports. Assessors scored the results according to predefined evaluation criteria. RESULTS Half of the participants (49.3%) had completely implemented the new test requirements (codons 12, 13, 59, 61, 117, and 146 of KRAS and NRAS), and 96 laboratories (73.3%) made no genotype mistakes. Correct nomenclature, according to the Human Genome Variation Society, was used by 82 laboratories (62.6%). CONCLUSION Although regulations were effective for several months, many laboratories were not ready for full RAS testing in the context of anti-EGFR therapy. Nevertheless, in each participating country, there are laboratories that provide complete and correct testing. External quality assessments can be used to monitor implementation of new test regulations and to stimulate the laboratories to improve their testing procedures. Because the results of this program are available on the website of the European Society of Pathology, patients and clinicians can refer test samples to a reliable laboratory.

Higher Quality of Molecular Testing, an Unfulfilled Priority: Results from External Quality Assessment for KRAS Mutation Testing in Colorectal Cancer

Precision medicine is now a key element in clinical oncology. RAS mutational status is a crucial predictor of responsiveness to anti-epidermal growth factor receptor agents in metastatic colorectal cancer. In an effort to guarantee high-quality testing services in molecular pathology, the European Society of Pathology has been organizing an annual KRAS external quality assessment program since 2009. In 2012, 10 formalin-fixed, paraffin-embedded samples, of which 8 from invasive metastatic colorectal cancer tissue and 2 artificial samples of cell line material, were sent to more than 100 laboratories from 26 countries with a request for routine KRAS testing. Both genotyping and clinical reports were assessed independently. Twenty-seven percent of the participants genotyped at least 1 of 10 samples incorrectly. In total, less than 5% of the distributed specimens were genotyped incorrectly. Genotyping errors consisted of false negatives, false positives, and incorrectly genotyped mutations. Twenty percent of the laboratories reported a technical error for one or more samples. A review of the written reports showed that several essential elements were missing, most notably a clinical interpretation of the test result, the method sensitivity, and the use of a reference sequence. External quality assessment serves as a valuable educational tool in assessing and improving molecular testing quality and is an important asset for monitoring quality assurance upon incorporation of new biomarkers in diagnostic services.

The relevance of external quality assessment for molecular testing for ALK positive non-small cell lung cancer: results from two pilot rounds show room for optimization.

Background and Purpose Molecular profiling should be performed on all advanced non-small cell lung cancer with non-squamous histology to allow treatment selection. Currently, this should include EGFR mutation testing and testing for ALK rearrangements. ROS1 is another emerging target. ALK rearrangement status is a critical biomarker to predict response to tyrosine kinase inhibitors such as crizotinib. To promote high quality testing in non-small cell lung cancer, the European Society of Pathology has introduced an external quality assessment scheme. This article summarizes the results of the first two pilot rounds organized in 2012–2013. Materials and Methods Tissue microarray slides consisting of cell-lines and resection specimens were distributed with the request for routine ALK testing using IHC or FISH. Participation in ALK FISH testing included the interpretation of four digital FISH images. Results Data from 173 different laboratories was obtained. Results demonstrate decreased error rates in the second round for both ALK FISH and ALK IHC, although the error rates were still high and the need for external quality assessment in laboratories performing ALK testing is evident. Error rates obtained by FISH were lower than by IHC. The lowest error rates were observed for the interpretation of digital FISH images. Conclusion There was a large variety in FISH enumeration practices. Based on the results from this study, recommendations for the methodology, analysis, interpretation and result reporting were issued. External quality assessment is a crucial element to improve the quality of molecular testing.

Endorsing good quality assurance practices in molecular pathology: risks and recommendations for diagnostic laboratories and external quality assessment providers

Quality assurance is an indispensable element in a molecular diagnostic laboratory. The ultimate goal is to warrant patient safety. Several risks that can compromise high quality procedures are at stake, from sample collection to the test performed by the laboratory, the reporting of test results to clinicians, and the organization of effective external quality assessment schemes. Quality assurance should therefore be safeguarded at each level and should imply a holistic multidisciplinary approach. This review aims to provide an overview of good quality assurance practices and discusses certain risks and recommendations to promote and improve quality assurance for both diagnostic laboratories and for external quality assessment providers. The number of molecular targets is continuously rising, and new technologies are evolving. As this poses challenges for clinical implementation and increases the demand for external quality assessment, the formation of an international association for improving quality assurance in molecular pathology is called for.

A stitch in time saves nine: external quality assessment rounds demonstrate improved quality of biomarker analysis in lung cancer

Biomarker analysis has become routine practice in the treatment of non-small cell lung cancer (NSCLC). To ensure high quality testing, participation to external quality assessment (EQA) schemes is essential. This article provides a longitudinal overview of the EQA performance for EGFR, ALK, and ROS1 analyses in NSCLC between 2012 and 2015. The four scheme years were organized by the European Society of Pathology according to the ISO 17043 standard. Participants were asked to analyze the provided tissue using their routine procedures. Analysis scores improved for individual laboratories upon participation to more EQA schemes, except for ROS1 immunohistochemistry (IHC). For EGFR analysis, scheme error rates were 18.8%, 14.1% and 7.5% in 2013, 2014 and 2015 respectively. For ALK testing, error rates decreased between 2012 and 2015 by 5.2%, 3.2% and 11.8% for the fluorescence in situ hybridization (FISH), FISH digital, and IHC subschemes, respectively. In contrast, for ROS1 error rates increased between 2014 and 2015 for FISH and IHC by 3.2% and 9.3%. Technical failures decreased over the years for all three markers. Results show that EQA contributes to an ameliorated performance for most predictive biomarkers in NSCLC. Room for improvement is still present, especially for ROS1 analysis.

ISO 15189-accredited laboratories fulfill the JCI Hospital Accreditation Standard requirements for the use of referral laboratories: report of a consensus meeting

AbstractAccreditation of healthcare services is recommended to ensure operation according to the highest quality standards. Various initiatives, such as legislation or accreditation by ISO or JCI, may be active to support and improve quality. The growing trend toward JCI hospital accreditation raised the concern of redundancy between JCI requirements for the use of referral laboratories and the ISO 15189 accreditation for medical laboratories. This would result in needless administrative efforts for hospital laboratories to collect and maintain required documentation, as the JCI quality requirements would be guaranteed given that the referral laboratory is ISO 15189 accredited for those examinations. A consensus meeting was organized by the Working Group for Hospital Accreditation of the Belgian Zorgnet-Icuro network, the University Hospitals of Leuven and the Red Cross to discuss the avoidance of any redundancy between both standards and to issue best practice guidelines for referral laboratories. It was concluded that JCI measurable elements for referral laboratories are covered by the ISO 15189 accreditation scope. The article substantiates the consensus that JCI and ISO quality requirements are harmonized and that accurate knowledge and interpretation of prevailing quality standards are essential to avoid redundancy in quality measures.

137INIMPORTANCE OF EXTERNAL QUALITY ASSESSEMENT IN IMMUNO-ONCOLOGY

ABSTRACT The important role of immunohistochemistry (IHC) is well known. IHC will recognize antigens and, consequently, identify and classify specific cells within a cell population whose morphology is heterogenous or apparently homogenous. Since many years external quality assessment (EQA) schemes for IHC are organized by NORDIQC and UK NEAQS. Since some years, IHC can be used for treatment selection in advanced NSCLC. In 2012, the European Society of Pathology (ESP) proposed an EQA scheme to promote high quality biomarker testing in NSCLC for EGFR mutation analysis and ALK rearrangement detection (IHC, FISH). From 2014 on, ROS1 testing is also included. The scheme aims to assess and improve the current status of testing in NSCLC, to provide education and remedial measures, to permit inter-laboratory comparison and to allow validation of test methods by distributing validated material harboring well-defined aberrations. In total, 173 different laboratories participated in the pilot rounds. In the first round, 29 laboratories submitted results for ALK IHC. In the second round, 58 laboratories submitted results for ALK IHC. If carefully clinically validated according to ISO 15189, ALK IHC may be considered as a screening method to select specimens for ALK FISH testing. In the context that at the time of the pilot studies no interlaboratory comparison validation studies were available, ALK IHC performance from our study shows that IHC testing is well implemented. Not surprisingly however, the error rates for IHC were greater than for FISH. Our study demonstrates improvement of ALK testing after only two rounds. It is expected that larger datasets, spanning a larger number of EQA participations will demonstrate a statistically significant improvement in performance. On scheme level, the decreased error rates in the second round demonstrated improvement for both ALK FISH and ALK IHC. Error rates for ALK FISH TMA and ALK IHC were still high (>5%), which stresses the need for continued education through EQA. Based on the results from this study, recommendations for the methodology, analysis, interpretation and result reporting were issued. External quality assessment is a crucial element to improve the quality of molecular testing. Disclosure: All authors have declared no conflicts of interest.