The Molecular Tumor Board of the Regina Elena National Cancer Institute: from accrual to treatment in real-world
Authors: Giacomini Patrizio , Valenti Fabio , Allegretti Matteo , Pallocca Matteo , De Nicola Francesca , Ciuffreda Ludovica , Fanciulli Maurizio , Scalera Stefano , Buglioni Simonetta , Melucci Elisa , Casini Beatrice , Carosi Mariantonia , Pescarmona Edoardo , Giordani Elena , Sperati Francesca , Jannitti Nicoletta , Betti Martina , Maugeri-Saccà Marcello , Cecere Fabiana Letizia , Villani Veronica , Pace Andrea , Appetecchia Marialuisa , Vici Patrizia , Savarese Antonella , Krasniqi Eriseld , Ferraresi Virginia , Russillo Michelangelo , Fabi Alessandra , Landi Lorenza , Minuti Gabriele , Cappuzzo Federico , Zeuli Massimo , Ciliberto Gennaro 
Published: October 2023

Abstract
Background
Molecular Tumor Boards (MTB) operating in real-world have generated limited consensus on good practices for accrual, actionable alteration mapping, and outcome metrics. These topics are addressed herein in 124 MTB patients, all real-world accrued at progression, and lacking approved therapy options.

Methods
Actionable genomic alterations identified by tumor DNA (tDNA) and circulating tumor DNA (ctDNA) profiling were mapped by customized OncoKB criteria to reflect diagnostic/therapeutic indications as approved in Europe. Alterations were considered non-SoC when mapped at either OncoKB level 3, regardless of tDNA/ctDNA origin, or at OncoKB levels 1/2, provided they were undetectable in matched tDNA, and had not been exploited in previous therapy lines.

Results
Altogether, actionable alterations were detected in 54/124 (43.5%) MTB patients, but only in 39 cases (31%) were these alterations (25 from tDNA, 14 from ctDNA) actionable/unexploited, e.g. they had not resulted in the assignment of pre-MTB treatments. Interestingly, actionable and actionable/unexploited alterations both decreased (37.5% and 22.7% respectively) in a subset of 88 MTB patients profiled by tDNA-only, but increased considerably (77.7% and 66.7%) in 18 distinct patients undergoing combined tDNA/ctDNA testing, approaching the potential treatment opportunities (76.9%) in 147 treatment-naïve patients undergoing routine tDNA profiling for the first time. Non-SoC therapy was MTB-recommended to all 39 patients with actionable/unexploited alterations, but only 22 (56%) accessed the applicable drug, mainly due to clinical deterioration, lengthy drug-gathering procedures, and geographical distance from recruiting clinical trials. Partial response and stable disease were recorded in 8 and 7 of 19 evaluable patients, respectively. The time to progression (TTP) ratio (MTB-recommended treatment vs last pre-MTB treatment) exceeded the conventional Von Hoff 1.3 cut-off in 9/19 cases, high absolute TTP and Von Hoff values coinciding in 3 cases. Retrospectively, 8 patients receiving post-MTB treatment(s) as per physician’s choice were noted to have a much longer overall survival from MTB accrual than 11 patients who had received no further treatment (35.09 vs 6.67 months, p = 0.006).

Conclusions
MTB-recommended/non-SoC treatments are effective, including those assigned by ctDNA-only alterations. However, real-world MTBs may inadvertently recruit patients electively susceptible to diverse and/or multiple treatments.