The aim of molecular tumor board (MTB) is to identify potential therapeutic strategies, based on genetic analysis, for patients (pts) not responding to standard therapies. All tumor types are eligible for MTB discussion and sarcomas are one of common target due to low number of standard and innovative treatments. Here we analyze the role of MTB in a sarcoma referral center.
We presented data from MTB including pts affected by soft tissue (STS) and bone sarcoma (BS) followed at Regina Elena National Cancer Institute in Rome and discussed from Dec 2019 to May 2022.
We discussed 19 pts affected by STS (14 pts) and BS (5 pts). FoundationOne was performed in 74%, Archer FusionPlex Sarcoma Panel in 37%, DNA Focus Assay in 26%, Whole exome sequencing in 26%, Oncomine Comprehensive Assay Plus in 16%, Promega MSI PCR Testing Kit in 16% and immunohistochemistry for PD-L1 in 16% of pts. Techniques were chosen depending on the type of kit available, the cost, the alterations searched and the time to obtain results. Druggable targets were found in 11 pts: mTOR mutation (m), HGF amplification (amp), ATM splice site m, MET amp, KRAS m, CDK4 amp, MYC amp, PTCH1 m, PIK3CA m, MDM4 amp and PD-L1 overexpression. Three patients (16%) received precision therapy: Imatinib and everolimus for mTOR m in cordoma, Cabozantinib for HGF amp in osteosarcoma and Pembrolizumab in angiosarcoma with PD-L 1 >10%. Eight pts continued standard therapy due to maintenance of response (5 pts) or to absence of literature supporting target treatment (3 pts). Molecular analysis allowed reformulation of diagnosis for one patient due to the presence of EWSR1-CREB3L2 fusion, typical of low-grade fibromyxoid sarcoma, that led to a histology-based treatment choice. Four patients were addressed to best supportive care (21%) while 2 pts (10,5 %) died.
MTB could be an effective tool for decision-making in sarcoma, but the lack of literature data and drug access hinder treatment choice. Enrollment in clinical trials could lead to overcome the problem. Moreover, the timing for requesting molecular analyses, at diagnosis or at the end of standard therapies, needs to be defined, considering both the tumor heterogeneity and the delay in obtaining results and starting treatment.
Regina Elena National Cancer Institute.
Has not received any funding.
All authors have declared no conflicts of interest.