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

Autor: Giacomini P; Clinical Trial Center, Biostatistics and Bioinformatics, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy. patrizio.giacomini@ifo.it., Valenti F; UOC Translational Oncology Research, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy., Allegretti M; UOC Translational Oncology Research, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy., Pallocca M; Clinical Trial Center, Biostatistics and Bioinformatics, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy., De Nicola F; SAFU, Department of Research, Advanced Diagnostics, and Technological Innovation, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy., Ciuffreda L; SAFU, Department of Research, Advanced Diagnostics, and Technological Innovation, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy., Fanciulli M; SAFU, Department of Research, Advanced Diagnostics, and Technological Innovation, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy., Scalera S; Clinical Trial Center, Biostatistics and Bioinformatics, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy., Buglioni S; Department of Pathology, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy., Melucci E; Department of Pathology, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy., Casini B; Department of Pathology, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy., Carosi M; Department of Pathology, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy., Pescarmona E; Department of Pathology, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy., Giordani E; UOC Translational Oncology Research, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy., Sperati F; Clinical Trial Center, Biostatistics and Bioinformatics, San Gallicano Dermatological Institute IRCCS, 00144, Rome, Italy., Jannitti N; Pharmacy Unit, Medical Direction, IRCCS-Regina Elena National Cancer Institute and San Gallicano Institute, 00144, Rome, Italy., Betti M; Clinical Trial Center, Biostatistics and Bioinformatics, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy., Maugeri-Saccà M; Clinical Trial Center, Biostatistics and Bioinformatics, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy.; Medical Oncology 2, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy., Cecere FL; Medical Oncology 2, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy., Villani V; Neuro-Oncology Unit, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy., Pace A; Neuro-Oncology Unit, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy., Appetecchia M; Oncological Endocrinology Unit, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy., Vici P; Phase IV Studies, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy., Savarese A; Medical Oncology 1, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy., Krasniqi E; Phase IV Studies, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy., Ferraresi V; Sarcomas and Rare Tumors Departmental Unit, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy., Russillo M; Sarcomas and Rare Tumors Departmental Unit, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy., Fabi A; Precision Medicine Unit in Senology, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168, Rome, Italy., Landi L; Clinical Trial Center: Phase 1 and Precision Medicine, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy., Minuti G; Clinical Trial Center: Phase 1 and Precision Medicine, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy., Cappuzzo F; Medical Oncology 2, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy., Zeuli M; Clinical Trial Center, Biostatistics and Bioinformatics, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy.; Medical Oncology 1, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy., Ciliberto G; Scientific Direction, IRCCS-Regina Elena National Cancer Institute, 00144, Rome, Italy.
Jazyk: angličtina
Zdroj: Journal of translational medicine [J Transl Med] 2023 Oct 16; Vol. 21 (1), pp. 725. Date of Electronic Publication: 2023 Oct 16.
DOI: 10.1186/s12967-023-04595-5
Abstrakt: 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.
(© 2023. BioMed Central Ltd., part of Springer Nature.)
Databáze: MEDLINE
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