Prognostic; Therapeutic management

The Personalis NeXT Dx Test, based on the NeXT platform, should be considered when personalized therapeutic guidance is sought for patients with cancer. The NeXT Dx test is indicated for use on solid tumors where its required to send FFPE tumor tissue along with matched normal (blood or saliva), where … The Personalis NeXT Dx Test, based on the NeXT platform, should be considered when personalized therapeutic guidance is sought for patients with cancer. The NeXT Dx test is indicated for use on solid tumors where its required to send FFPE tumor tissue along with matched normal (blood or saliva), where samples are reviewed and selected by a pathologist as the most representative block for the patient’s diagnosis. The intended use of the NeXT Dx test is in-line with the rationale for molecular testing of cancers described in “Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists” (PMID 27993330). Specifically, the NeXT Dx test should be used in situations where a more complete knowledge of the molecular alteration status of a cancer may assist in making clinical diagnosis and treatment decisions, determining prognosis, and determining patient eligibility for clinical trials. View more

Guidance for management

Patients with all solid tumors

NeXT Dx

Tests performed
Entire test performed in-house

The NeXT Dx test exhibits a median depth of >500X over the exome footprint for estimating tumor mutational burden (TMB), and >1500X over the coding and relevant non-coding regions of 247 genes via Illumina next generation sequencing. Matched normal samples are sequenced at ~150x depth. NeXT Dx demonstrates high analytical … The NeXT Dx test exhibits a median depth of >500X over the exome footprint for estimating tumor mutational burden (TMB), and >1500X over the coding and relevant non-coding regions of 247 genes via Illumina next generation sequencing. Matched normal samples are sequenced at ~150x depth. NeXT Dx demonstrates high analytical sensitivity to genetic alterations that are known targets or modifiers of treatment or are suspected biomarkers of progression in cancer. Test performance specifications were determined by performing a large-scale validation study of the NeXT Dx platform. A large collection of cancer cell lines, constructs, CAP proficiency, and remnant clinical samples were used to validate exome footprint. Results were compared with a validated TSO500 test. Overall sensitivity was high among a broad set of tumor types with previously documented genetic aberrations, and varied according to the type of genetic alteration: Small nucleotide variants (at >/= 5% mutant allele frequency): >99%; Small insertions and deletions (at >/= 5% mutation allele frequency): 98.2%; Copy number alterations (at >/= 30% tumor content): 98%; Fusions: 95.8%. Specificity, estimated by positive predictive value (PPV) was >99%. In addition, the Personalis NeXT Dx Test provides an estimate of tumor mutation burden (TMB) and microsatellite instability (MSI) status. Microsatellite instability (MSI) status is determined by measuring nucleotide repeats at 117 loci. MSI validation demonstrated a concordance of 99% at a minimum of 20% tumor content. Estimation of TMB is evaluated across the exome by measuring the number of non-synonymous, somatic coding mutations, and is reported as the number of mutations per megabase (muts/Mb). View more

NeXT Dx is indicated for use on solid tumors . This test will report germline mutations in a subset of genes as incidental findings therefore confirmatory testing will be required. The test is not designed for expression profiling.

Is proficiency testing performed for this test? Help
Yes

Method used for proficiency testing: Help
Formal PT program

PT Provider: Help
American College of Medical Genetics / College of American Pathologists, ACMG/CAP

Description of PT method: Help
The Multigene Tumor Panel (MTP), NGS solid tumor (NGSST), and Fusion RNA proficiency tests are performed biannually through the College of American Pathologists (CAP). Biannual proficiency testing for copy number alterations is performed in-house.