From seed to harvest: 18-month experience of molecular tumor board (MTB)-based precision oncology practice at the Verona University Hospital.
Authors: Rossi Alice , Trevisani Elena , Riva Silvia , Reni Anna , Mafficini Andrea , Luchini Claudio , Sganzerla Federico , Piacentini Michela , Pasqualin Luca , Rota Michele , Avesani Barbara , Melisi Davide , Tondulli Luca , Auriemma Alessandra , Menis Jessica , Cingarlini Sara , Atsina Francesca Mansa , Lawlor Rita T. , Scarpa Aldo , Milella Michele 
Published: June 2023

e15065 Background: Next generation Sequencing (NGS) allows the identification of potentially actionable molecular alterations that may constitute a therapeutic opportunity beyond standard systemic treatments for advanced cancer patients (pts). The interpretation of NGS profiling and its introduction in clinical practice can be guided by systematic implementation of Molecular Tumor Board (MTB). Methods: Between May 2020 and January 2023, 663 cancer pts accessed NGS profiling, in the context of investigator-driven and/or industry-sponsored research programs, using the CORE panel (in-house developed in collaboration with the International Cancer Genome Consortium - ICGC, covering 174 clinically relevant genes, structural variations and genomic signatures; 411 pts) and commercial FoundationOne CDx or FoundationOne Liquid assays (131 and 27 respectively). Pts with potentially clinically relevant molecular alterations were prescreened by Pathology and Oncology dedicated professionals and within multidisciplinary disease-oriented teams. Here we describe the results of MTB discussions at the Verona University Hospital. Results: Sixty-seven pts (10% of those profiled) were discussed at MTB bi-weekly meetings, between July 2021 and January 2023. Further diagnostic tests were requested in 19 pts (28%; IHC: 7, molecular analyses: 10, re-biopsies: 3). In 1 case histological diagnosis was changed upon re-biopsy (acinar pancreatic cancer to breast cancer NOS). Oncogenetic counselling was proposed in 10 pts (15%). Forty pts (60% of those discussed) were deemed eligible for NGS-informed treatment. Among these, twenty-two pts (55%) did not start MTB-indicated therapy, due to currently non-progressive disease (11), clinical deterioration (7), other Center referral (3) or refusal (1). Eighteen pts (45%) started MTB-recommended therapy in first (17%), second (28%) or > = third line (55%). Treated pts were affected by rare tumors (8), pancreatic cancer (5), NSCLC (2), biliary tract, colon, and breast cancer (1 patient each). Types of treatment were: 12 targeted-, 2 immuno-, 2 chemo-, 2 combined-therapies. Among twelve evaluable pts, one complete response (8%), seven partial responses (58%), two stable (16%) and two progressive diseases (16%) were observed (RECIST v1.1); median PFS in treated pts was 12.7 [0.1-17.7] months. Five pts (41%) are currently awaiting response evaluation. Conclusions: Systematic identification and discussion of potentially actionable gene alterations brought to NGS-informed, MTB-endorsed therapeutic indications in 6% of profiled pts, 65% of whom experienced relevant clinical benefit from treatment. Increased and timely (preferably at diagnosis) access to NGS profiling, revised criteria for and more extensive MTB discussions should be implemented to increase the impact of Precision Oncology practices on pts' outcome.