A Comprehensive Tumor Molecular Profile Analysis in Clinical Practice: A Single Center’s Experience

Abstract Background: Tumor molecular profile is of great importance for the detection of biomarkers of response to targeted treatment due to the increased availability, with concomitant reduction of cost, of Next Generation Sequencing technology (NGS). In parallel to 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.Methods: In the present study, a 161 gene NGS panel, containing the majority of clinically significant genes for cancer treatment selection, was used for tumor molecular profile analysis. 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.Results: Molecular profile analysis was conducted in 610 cancer patients, while in 393 of them a at least one biomarker for immunotherapy response was requested. At least one actionable alteration was detected in 77.70% of the patients. 54.59% 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 22.40%, while an option for on-label or off-label treatment was provided in 71.35% of the cases. Conclusions: Tumor molecular profile analysis by NGS is a first-tier methodology for a variety of tumor types, which provides critical information for treatment decision making in cancer patients. Importantly, simultaneous analysis for targeted therapy and immunotherapy biomarkers could lead to a better tumor characterization and provide actionable information in the majority of patients. Moreover, our results indicate that one in two patients is eligible for ICI treatment based on the biomarkers’ analysis. However, when these analyses are performed, the challenge is their implementation in clinical practice. Multidisciplinary patient management is critical to the refinement of the strategy incorporating such information.