Comprehensive tumor molecular profile analysis in clinical practice

• Published in: BMC medical genomics Vol. 14; no. 1; pp. 105 - 21
• Main Authors: Özdoğan, Mustafa, Papadopoulou, Eirini, Tsoulos, Nikolaos, Tsantikidi, Aikaterini, Mariatou, Vasiliki-Metaxa, Tsaousis, Georgios, Kapeni, Evgenia, Bourkoula, Evgenia, Fotiou, Dimitrios, Kapetsis, Georgios, Boukovinas, Ioannis, Touroutoglou, Nikolaos, Fassas, Athanasios, Adamidis, Achilleas, Kosmidis, Paraskevas, Trafalis, Dimitrios, Galani, Eleni, Lypas, George, Orhan, Bülent, Tansan, Sualp, Özatlı, Tahsin, Kırca, Onder, Çakır, Okan, Nasioulas, George
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 14-04-2021; BioMed Central; BMC
• Subjects: Adult; Aged; Aged, 80 and over; B7-H1 Antigen - genetics; B7-H1 Antigen - metabolism; Biological markers; Biomarkers; Biomarkers, Tumor - genetics; Cancer therapies; Care and treatment; Clinical medicine; Clinical trials; Decision making; Deoxyribonucleic acid; Diagnosis; DNA; DNA sequencing; FDA approval; Female; Genes; Genetic aspects; High-Throughput Nucleotide Sequencing; Humans; Identification and classification; Immunotherapy; Lung cancer; Male; Medical prognosis; Metastasis; Microsatellite Instability; Middle Aged; Molecular diagnostic techniques; Molecular profile; Mutation; Neoplasms - genetics; Neoplasms - therapy; Next Generation Sequencing; Nucleotide sequencing; Pancreatic cancer; Patients; PD-L1; PD-L1 protein; Software; Targeted treatment; Tumor mutation burden; Tumors; Greece; Targeted treatment; Immunotherapy; Tumor mutation burden; Molecular profile; PD-L1; Microsatellite instability; Next Generation Sequencing
• ISSN: 1755-8794; 1755-8794
• DOI: 10.1186/s12920-021-00952-9

Tumor molecular profile analysis by Next Generation Sequencing technology is currently widely applied in clinical practice and has enabled the detection of predictive biomarkers of response to targeted treatment. In parallel with targeted therapies, immunotherapies are also evolving, revolutionizing cancer therapy, with Programmed Death-ligand 1 (PD-L1), Microsatellite instability (MSI), and Tumor Mutational Burden (TMB) analysis being the biomarkers employed most commonly.
In the present study, tumor molecular profile analysis was performed using a 161 gene NGS panel, containing the majority of clinically significant genes for cancer treatment selection. A variety of tumor types have been analyzed, including aggressive and hard to treat cancers such as pancreatic cancer. Besides, the clinical utility of immunotherapy biomarkers (TMB, MSI, PD-L1), was also studied.
Molecular profile analysis was conducted in 610 cancer patients, while in 393 of them a at least one biomarker for immunotherapy response was requested. An actionable alteration was detected in 77.87% of the patients. 54.75% of them received information related to on-label or off-label treatment (Tiers 1A.1, 1A.2, 2B, and 2C.1) and 21.31% received a variant that could be used for clinical trial inclusion. The addition to immunotherapy biomarker to targeted biomarkers' analysis in 191 cases increased the number of patients with an on-label treatment recommendation by 22.92%, while an option for on-label or off-label treatment was provided in 71.35% of the cases.
Tumor molecular profile analysis using NGS is a first-tier method for a variety of tumor types and provides important information for decision making in the treatment of cancer patients. Importantly, simultaneous analysis for targeted therapy and immunotherapy biomarkers could lead to better tumor characterization and offer actionable information in the majority of patients. Furthermore, our data suggest that one in two patients may be eligible for on-label ICI treatment based on biomarker analysis. However, appropriate interpretation of results from such analysis is essential for implementation in clinical practice and accurate refinement of treatment strategy.