Home 5 Diagnostic Testing and Emerging Technologies 5 New EMSO Guidelines Address Efficacy of Next Generation Sequencing for Different Cancer Types

New EMSO Guidelines Address Efficacy of Next Generation Sequencing for Different Cancer Types

by | Nov 2, 2020

The European Society for Medical Oncology (ESMO) recently issued guidelines on use of next-generation sequencing (NGS) for various types of cancer as part of routine clinical practice. The guidelines also address whether broad-based NGS should replace small panels designed to test a single gene or a group of genes. The ESMO guidelines are the first […]

The European Society for Medical Oncology (ESMO) recently issued guidelines on use of next-generation sequencing (NGS) for various types of cancer as part of routine clinical practice. The guidelines also address whether broad-based NGS should replace small panels designed to test a single gene or a group of genes. The ESMO guidelines are the first recommendations from a scientific society on the use of NGS. Their objective is to “unify decision-making about how NGS should be used for patients with metastatic cancer.” The Diagnostic Challenge NGS is a high throughput technique that uses DNA sequencing technologies capable of deciphering multiple nucleotide sequences at the same time. NGS is used for cancer treatment and its effectiveness depends in large part on tumor type and the efficacy and availability of targeted drugs. Routine Use of NGS by Cancer Type The new guidelines, published in Annals of Oncology, address the eight cancers responsible for the most deaths worldwide as well as additional cancers for which routine NGS may be justified based on the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT), which ranks molecular targets and their respective treatments on four levels. The authors also considered cost-effectiveness research regarding the use of multigene sequencing. For advanced, non-squamous NSCLC, the guidelines recommend routine use of RNA- or DNA-based NGS to detect mutations and fusions with ESCAT level I matches. Broad-based NGS could also be used routinely to detect alterations with lower than level I matches, but only when specific agreements are made with payors to consider the cost of testing versus small panels. For metastatic breast cancer, the guidelines say there is “currently no need to perform tumor multigene NGS in the context of daily practice.” Somatic testing cannot fully substitute germline testing for actionable BRCA mutations, they explained, and actionable PIK3CA mutations can be tested with polymerase chain reaction (PCR)-based assays instead. For metastatic colorectal cancer, the guidelines say that PCR and IHC can be used to detect level I mutations in KRAS, NRAS, and BRAF for which targeted treatments have demonstrated efficacy to highlight why routine multigene NGS is not necessary. However, PCR and IHC should be used as an alternative “only if it does not generate extra cost compared to standard techniques.” For advanced prostate cancer, the recommendations support routine NGS to assess somatic BRCA mutations in countries where PARP inhibitors are accessible. In addition, where broad-based testing is used, it should also include testing for AKT inhibitors, DNA repair genes and MSI signature, but broader panels should only be used in cases where payors agree it is cost effective. For metastatic gastric cancer, pancreatic cancer and hepatocellular carcinoma, the guidelines do not recommend multigene NGS, saying that “cheap standard methods” could be used to detect MSI or NTRK fusion status, for which immune checkpoint inhibitors and TRK inhibitors, respectively, may provide benefit. For metastatic cholangiocarcinoma and ovarian cancer, routine multigene NGS is recommended based on the presence of level I ESCAT matches, as well as for cancers of unknown primary, despite the absence of level I matches. Other cancers: The guidelines also recommended NGS for TMB testing in cervical cancer, well- and moderately- differentiated neuroendocrine tumors, salivary cancers, vulvar cancers, and thyroid cancers. Beyond these tumor types, the evidence was not strong enough to justify routine TMB testing. For tumor-agnostic approvals of several TRK inhibitors for NTRK fusion-positive cancers, the authors recommended that NGS should only be used to detect NTRK fusions, which have a very low incidence, in cancers where the technology is otherwise recommended.    

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