Abstract

Cancer is a multifactorial genetic disease: NGS-based broad genomic profiling allows the identification of potential molecular drivers. Evaluation of the clinical actionability of NGS results should be guided by the expert consensus of a MTB, providing management recommendations and translating molecular alterations into clinical indications. Here we describe the MTB experience at the Verona University Hospital. Between Feb 2021 and Mar 2022, 315 patients (pts) with advanced solid malignancies deemed orphan with respect to established molecular diagnostics and availability of standard molecularly targeted treatments, had access to somatic profiling using targeted NGS panels. NGS results were discussed at bi-weekly MTB meetings, encompassing oncologists, pathologists, geneticists, pharmacologists, and pharmacists. The three most represented primary tumors were pancreatic (30%), breast (16%) and head and neck (14%) cancers. Among 315 pts profiled (13% of the annual active oncological population at our Center), 42 were discussed at MTB meetings, so far: 15 patients (36%) received a treatment recommendation: 4 within an ongoing clinical trial, 11 through atypical drug access (authorized off label use, named patient programs and other access schemes). Six pts (14%) were referred for genetic counseling, based on evidence of potential germline alterations at somatic testing. Further molecular investigations were requested/proposed in 11 pts (26%): IHC in 5, germline testing in 5, and a second NGS test + IHC in 1 pt, respectively. NGS-based profiling is a comprehensive tool to identify potentially actionable targets in advanced solid tumors. Its systematic application may have a profound impact on individual pts clinical course and outcomes. MTB discussion successfully provided suitable management strategies in a significant fraction of pts. Based on the careful definition of the criteria for accessing NGS profiling and the consequent MTB discussion, such approach should become a constitutive part of the oncological care program in the era of precision medicine.

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