Journal Article

The Molecular Tumor Board of the Regina Elena National Cancer Institute: from accrual to treatment in real-world

Allegretti, Matteo, Betti, Martina, Ciuffreda, Ludovica, Ciliberto, Gennaro, Maugeri-Saccà, Marcello, Villani, Veronica, Carosi, Mariantonia, Cecere, Fabiana Letizia, Giordani, Elena, Fabi, Alessandra, Pallocca, Matteo, Buglioni, Simonetta, Fanciulli, Maurizio, Russillo, Michelangelo, Minuti, Gabriele, Landi, Lorenza, Scalera, Stefano, Savarese, Antonella, Sperati, Francesca, Jannitti, Nicoletta, De Nicola, Francesca, Pace, Andrea, Valenti, Fabio, Melucci, Elisa, Krasniqi, Eriseld, Casini, Beatrice, Zeuli, Massimo, Ferraresi, Virginia, Pescarmona, Edoardo, Vici, Patrizia, Appetecchia, Marialuisa, Cappuzzo, Federico, Giacomini, Patrizio

2023

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Analysis / Biomedical and Life Sciences / Biomedicine / Cancer / Cancer therapies / Care and treatment / Circulating tumor DNA (ctDNA) / Clinical deterioration / Clinical trials / Development and progression / Digital PCR (dPCR) / DNA fingerprinting / DNA sequencing / Emerging Therapeutics / Gene mapping / Genetic counseling / Genetic markers / Health care access / Medicine/Public Health / Molecular targeted therapy / Molecular tumor board / Next generation sequencing (NGS) / Nucleotide sequencing / Oncology / Patient outcomes / Patients / Target therapy / Tumor DNA (tDNA) / Tumors / Variables