Despite the rapid progress in the field of personalized medicine and the efforts to apply specific treatment strategies to patients based on the presence of pathogenic variants in one, two, or three genes, patient response to the treatment in terms of positive benefit and overall survival remains heterogeneous. However, advances in sequencing and bioinformatics technologies have facilitated the simultaneous examination of somatic variants in tens to thousands of genes in tumor tissue, enabling the determination of personalized management based on the patient's comprehensive genomic profile (CGP). CGP has the potential to enhance clinical decision-making and personalize innovative treatments for individual patients, by providing oncologists with a more comprehensive molecular characterization of tumors. This study aimed to highlight the utility of CGP in routine clinical practice. Here we present three patient cases with various advanced cancer indicated for CGP analysis using a combination of SOPHiA Solid Tumor Solution (STS, 42 genes) for DNA and SOPHiA RNAtarget Oncology Solution (ROS, 45 genes and 17 gene fusions with any random partners) for RNA. We were able to identify actionable genomic alterations in all three cases, thereby presenting valuable information for future management of these patients. This approach has the potential to transform clinical practice and greatly improve patient outcomes in the field of oncology.

• MeSH
• Genomics MeSH
• Precision Medicine MeSH
• Humans MeSH
• Neoplasms * diagnosis   genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

The diagnostic work-up for non-small cell lung cancer (NSCLC) requires biomarker testing to guide therapy choices. This article is the second of a two-part series. In Part 1, we summarised evidence-based recommendations for obtaining and processing small specimen samples (i.e. pre-analytical steps) from patients with advanced NSCLC. Here, in Part 2, we summarise evidence-based recommendations relating to analytical steps of biomarker testing (and associated reporting and quality assessment) of small specimen samples in NSCLC. As the number of biomarkers for actionable (genetic) targets and approved targeted therapies continues to increase, simultaneous testing of multiple actionable oncogenic drivers using next-generation sequencing (NGS) becomes imperative, as set forth in European Society for Medical Oncology guidelines. This is particularly relevant in advanced NSCLC, where tissue specimens are typically limited and NGS may help avoid tissue exhaustion compared with sequential biomarker testing. Despite guideline recommendations, significant discrepancies in access to NGS persist across Europe, primarily due to reimbursement constraints. The use of increasingly complex testing methods also has implications for the reporting of results. Molecular testing reports should include clinical interpretation with additional commentary on sample adequacy as appropriate. Molecular tumour boards are recommended to facilitate the interpretation of complex genetic information arising from NGS, and to collaboratively determine the optimal treatment for patients with NSCLC. Finally, whichever testing modality is employed, it is essential that adequate internal and external validation and quality control measures are implemented.

• Keywords
• Best practice, External quality assessment, Liquid biopsy, Molecular diagnostics, Next-generation sequencing, Non-small cell lung carcinoma,
• MeSH
• Biomarkers MeSH
• Humans MeSH
• Mutation MeSH
• Lung Neoplasms * diagnosis   drug therapy   genetics   MeSH
• Carcinoma, Non-Small-Cell Lung * diagnosis   genetics   pathology   MeSH
• High-Throughput Nucleotide Sequencing methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Biomarkers MeSH