Testing Guidelines Address NGS, Cancer and Other Screenings

Guidelines at a Glance is a new feature from G2 Intelligence that surveys recent guidelines issued from the U.S. Preventive Services Task Force and diagnostics industry leaders such as the College of American Pathologists, the American Society for Clinical Pathology, Association for Molecular Pathology and others. You can review an archive of the guidelines covered in G2 publications at www.g2intelligence.com/guidelines. Here is a run down of some the most recent guidelines of interest to laboratories and pathologists.

Validation of Next-Generation Sequencing–Based Oncology Panels
A joint consensus recommendation of the Association for Molecular Pathology and College of American Pathologists published in the Journal of Molecular Diagnostics provides assistance to clinical laboratories with the validation and ongoing monitoring of next-generation sequencing-based testing for detection of somatic variants. The guideline seeks to ensure high quality of sequencing results of targeted gene panels and their diagnostic use in solid tumors and hematological malignancies.

Topics covered in the consensus recommendations include: next-generation sequencing-based test development, optimization, and validation. Specifically, it includes recommendations on panel content selection, utilization of reference materials for evaluation of assay performance, determining of positive percentage agreement and positive predictive value for each variant type, and requirements for minimal depth of coverage and minimum number of samples that should be used to establish test performance characteristics. The recommendations also discuss quality control metrics.

Expanded Carrier Screening for All Women
All women, regardless of ethnic background, should be offered expanded carrier screening prior to pregnancy, according to new recommendations published by the American College of Obstetricians and Gynecologists' Committee on Genetics. Ethnic-specific screening, pan-ethnic screening, and expanded carrier screening are all "acceptable" strategies that can be used to identify the risk of genetic disorders in potential offspring. Additionally, the committee's recommendations say:

• Providers should establish "a standard approach that is consistently offered," although the ultimate screening approach for an individual should also be guided by the patient's family history and personal values.

• Expanded carrier screening panels should include conditions that have a carrier frequency of 1 in 100 or greater, a well-defined phenotype, a detrimental effect on quality of life, cause cognitive or physical impairment, require surgical or medical intervention, or have an onset early in life.

• Regardless of ethnicity, screening strategy, or history, all patients should receive carrier screening for the following conditions: cystic fibrosis, spinal muscular atrophy, and thalassemias and hemoglobinopathies (plus a complete blood count).

Molecular Biomarkers for Colorectal Cancer
A joint guideline from the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology, published in the March issue of the Journal of Molecular Diagnostics establishes evidence-based recommendations for mutational testing of EGFR signaling pathways for patients with colorectal cancer (CRC), as well as key steps laboratories can take to operationalize CRC molecular testing.

A systematic literature review found evidence supporting mutational testing to guide therapy of CRC with anti-EGFR monoclonal antibodies. Mutations in BRAF and MMR have "clear prognostic value," while KRAS and NRAS have "relatively strong" evidence as negative predictors of benefit to anti-EGFR therapies. In addition to considerations for specific mutational analysis were recommendations for how laboratories can aid adoption of CRC molecular testing.

• Laboratories should use CRC molecular biomarker testing methods that are able to detect mutations with at least 5% mutant allele frequency.

• Laboratories should optimally utilize tissue specimens by using appropriate techniques (e.g., multiplexed assays).

• Laboratories must use validated CRC molecular biomarker testing methods with sufficient performance characteristics and must incorporate these methods into their overall laboratory quality improvement program.

• CRC molecular biomarker testing reports should include a results and interpretation section easily understandable by oncologists.

• It is suggested that 90% of reports be available within 10 working days from date of receipt in the molecular diagnostics laboratory.

• It is suggested that for laboratories requiring send-out testing, 90% of specimens should be sent out within 3 working days.

Update for Screening for Genital Herpes
An update on screening for genital herpes remains "consistent" with the previous 2005 U.S. Preventive Services Task Force (USPSTF) recommendations against routine serologic screening for genital herpes simplex virus (HSV) infection in asymptomatic adolescents and adults. The update, published in the Dec. 20, 2016 issue of the Journal of the American Medical Association, includes the recommendation to not screen asymptomatic, pregnant women.

"Based on the natural history of HSV infection, its epidemiology, and the available evidence on the accuracy of serologic screening tests, the USPSTF concluded that the harms outweigh the benefits of serologic screening for genital HSV infection," the task force writes.

Evidence Lacking to Evaluate Celiac Screening
The U.S. Preventive Services Task Force (USPSTF) found there is not enough evidence to advocate for or against screening asymptomatic adults, adolescents, and children for celiac disease, according to the recommendation, published March 28 in the Journal of the American Medical Association. The standard method of diagnosing celiac disease in symptomatic patients (older than 2 years) is the tissue transglutaminase IgA test, followed by intestinal biopsy for histologic confirmation.

The finding includes a lack of evidence for targeted screening of those that are asymptomatic, but at high risk for the disease due to family history or other autoimmune disorders. USPSTF reports inadequate evidence regarding the accuracy, effectiveness, and benefits/harms of screening with regard to morbidity, mortality, or quality of life. USPSTF suggests the need for future studies, particularly in high-risk populations, that randomly assign participants to screening or no screening to evaluate clinical outcomes.

First Diagnostic Criteria Established for Castleman Disease
Castleman Disease is a rare, complex disease that often looks similar to a lymphoma, but can present like an autoimmune or infectious disorder. Diagnosis is complicated by a lack of a biomarker, leading to a recent push to establish diagnostic criteria (evidence-based consensus), which were recently published in Blood. The criteria require multicentric lymphadenopathy with defined histopathology, two or more clinical/laboratory changes (elevated CRP or ESR, anemia, thrombocytopenia, hypoalbuminemia, renal dysfunction, and/or polyclonal hypergammaglobulinemia), and exclusion of mimic conditions (infectious, autoimmune, or malignant).