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The ESMO Precision Medicine Working Group (PMWG) first published its recommendations for when to use next-generation sequencing (NGS) in routine practice for patients with metastatic cancers in 20201. At that time, based on identification of recurrent genomic alterations in the eight most deadly cancers and their ranking on the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT), NGS was recommended for advanced non-squamous non-small-cell lung cancer (NSCLC), prostate cancer, ovarian cancer and cholangiocarcinoma. It was additionally noted as an alternative to PCR for advanced colorectal cancers.
Advances in precision medicine during the past four years have resulted in revised ESCAT rankings for a number of biomarkers, leading the PMWG to reconfirm their previous recommendations and to expand the set of metastatic cancers recommended for NGS testing. The recommendations now include NGS testing for advanced breast cancer as well as the following advanced rare cancers: gastrointestinal stromal tumor, soft-tissue sarcomas, thyroid cancer2.
Due to the potential of NGS to help identify the primary tumor, plus its positive impact on patient outcomes, the PMWG additionally recommends that NGS testing be performed for cancers of unknown primary.
In countries where targeted therapies are accessible, recommendations for NGS testing now further extend to detection of the following tumor-agnostic biomarkers:
The PMWG stresses the importance of carrying out NGS testing in clinical research centers as well as ensuring that the selected test includes the actionable biomarkers of interest. They specifically flag the importance of assessing the chosen assay for its ability to detect fusions and homologous recombination deficiency (HRD), when relevant, as not all assays have these capabilities. The PMWG also highlight the assay’s ability to identify clonal hematopoiesis (CH) as an important consideration. High-risk CH can be found in patients with solid tumors, especially when plasma cell-free DNA sequencing is performed. To be considered as CH of indeterminate potential (CHIP), the somatic variants of haematological malignancy-associated genes should be with a variant allele fraction (VAF) of ≥2%.
See the full set of guidelines here: ESMO Recommendations for the use of NGS for patients with advanced cancer.
At SOPHiA GENETICS, we offer solutions that cover the major biomarkers highlighted in the ESMO recommendations, including the key fusions noted above. Moreover, the PMWG recognizes SOPHiA DDM™ Dx HRD Solution as one of only a few methods validated for HRD detection in advanced ovarian cancer.
Additionally, we offer liquid biopsy and solid tumor applications that leverage a matched tumor-normal sequencing approach to identify CHIP and germline variants, revealing genomic alterations of true somatic origin. Recent ESMO guidelines on reporting genomic test results for solid cancers recommend that, when feasible and with proper consent, the NGS report should specify whether alterations are of germline versus somatic origin3. With matched tumor-normal sequencing, the germline origin of any variant can be determined with certainty3.
Read our flyer for further information on how SOPHiA DDM™ for Solid Tumors advances clinical research by aligning with guideline recommendations: View the flyer
References
Explore this infographic summary to learn more about the machine learning model developed by Margue et al. for the prediction of disease-free survival in patients undergoing surgery for renal cell carcinoma.
Margue G, et al. UroPredict: Machine learning model on real-world data for prediction of kidney cancer recurrence (UroCCR-120). NPJ Precis Oncol. 2024 Feb 23;8(1):45.
SOPHiA GENETICS multimodal analysis technology and concepts in development. May not be available for sale.
Explore this infographic summary to gain insights into the key findings from Pozzorini et al.’s publication on the GIIngerTM deep learning algorithm for prediction of HRD status and patient response to PARPi treatment in ovarian cancer.
Click here to read the full publication.
Pozzorini C, Andre G, Coletta C, et al. GIInger predicts homologous recombination deficiency and patient response to PARPi treatment from shallow genomic profiles. Cell Rep Med. 2023 Dec 19;4(12):101344. doi: 10.1016/j.xcrm.2023.101344.
GIInger™ data were generated using the SOPHiA DDM™ Dx HRD Solution, available as a CE-IVD product for In Vitro Diagnostic Use in European Economic Area (EEA), the United Kingdom and Switzerland . SOPHiA GENETICS products are for Research Use Only and not for use in diagnostic procedures unless specified otherwise.
Explore this infographic summary to discover the key findings from Janin et al.’s publication on next-generation sequencing (NGS) for the diagnosis of inherited cardiac diseases.
Click here to read the full publication.
Janin A, Januel L, Cazeneuve C, Delinière A, Chevalier P, Millat G. Molecular Diagnosis of Inherited Cardiac Diseases in the Era of Next-Generation Sequencing: A Single Center's Experience Over 5 Years. Mol Diagn Ther. 2021 May;25(3):373-385.
SOPHiA GENETICS products are for research use only – not for use in diagnostic procedures.
Dr. Mohamed Z Alimohamed kindly summarized his upcoming peer-reviewed publication in Gene:
“Current splice prediction algorithms have limited sensitivity and specificity, therefore many potential splice variants are classified as variants of uncertain significance (VUSs).
However, functional assessment of VUSs to test splicing is labor-intensive and time-consuming. We have developed a decision tree, SEPT-GD, by setting thresholds for the splice prediction programs implemented in Alamut™️ to prioritize potential splice variants associated with cardiomyopathies for functional studies, and functionally verified the outcome of the decision tree.
SEPT-GD outperforms the tools commonly used for RNA splicing prediction and improves prioritization of variants in cardiomyopathy genes for functional splicing analysis.”
Click here to read the full publication.
Alimohamed MZ, Boven LG, van Dijk KK, Vos YJ, Hoedemaekers YM, van der Zwaag PA, Sijmons RH, Jongbloed JDH, Sikkema-Raddatz B, Westers H. SEPT-GD: A decision tree to prioritise potential RNA splice variants in cardiomyopathy genes for functional splicing assays in diagnostics. Gene. 2023 Jan 30;851:146984.
Alamut™️ is for Research Use Only. Not for use in diagnostic procedures.
SOPHiA GENETICS products are for Research Use Only and not for use in diagnostic procedures unless specified otherwise.
SOPHiA DDM™ Dx Hereditary Cancer Solution, SOPHiA DDM™ Dx RNAtarget Oncology Solution and SOPHiA DDM™ Dx Homologous Recombination Deficiency Solution are available as CE-IVD products for In Vitro Diagnostic Use in the European Economic Area (EEA), the United Kingdom and Switzerland. SOPHiA DDM™ Dx Myeloid Solution and SOPHiA DDM™ Dx Solid Tumor Solution are available as CE-IVD products for In Vitro Diagnostic Use in the EEA, the United Kingdom, Switzerland, and Israel. Information about products that may or may not be available in different countries and if applicable, may or may not have received approval or market clearance by a governmental regulatory body for different indications for use. Please contact us at support@sophiagenetics.com to obtain the appropriate product information for your country of residence.
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