In recent years, all major cancer centers have instituted Molecular Tumor Boards (MTBs), multidisciplinary entities dedicated to identifying the most appropriate therapy for individual cancer patients.  They focus their attention exclusively (or predominantly) on selected cancer patients who have failed every previously approved line of therapy and have no other practicable options. Specifically, the MTB recommends the use of drugs not yet approved by regulatory agencies, as long as they are supported by solid clinical and molecular evidence. The MTB of the Regina Elena National Cancer Institute (IRE), officially active since September 2018, has established itself as a point of reference in the Lazio Region and systematically intervenes in the management of the treatment of complex intramural and external clinical cases. In this regard, the MTB -IRE has been working, in the last year, on a project of collaborations and shared knowledge across oncology-focused institutions active in different national realities, with the aim of enabling the dissemination of best practices in the management of personalized therapy in oncology without excluding the possibility of aggregation of external entities as well.

The MTB - IRE meets regularly every 15 days, and during the sessions the patients' clinical histories and molecular data compared with those in the scientific literature are discussed in order to issue a therapeutic recommendation with drugs possibly already in use, but with different indications in other tumor histotypes, drugs that in the near future may themselves become 'indicative' drugs in other diseases and specific nosological conditions.

The MTB - IRE, over the past few years (2018-2022), has evaluated the clinical history of more than 130 patients who received genomic profiling performed by different approaches: New Generation Sequencing (NGS), Whole Exome Sequencing (WES), assessment of circulating tumor DNA (ctDNA) levels. Analyzed patients, with actionable alterations, were treated according to MTB recommendations, obtaining significant positive results in terms of overall survival.

Importantly, all costs associated with the additional genomic analyses were fully supported by the Regina Elena Institute. None of the selected patients were required to pay for the molecular testing or for the purchase and administration of the drugs. In specific situations, when applicable, the MTB has engaged a collaborative effort with Italian national and local health authorities to obtain special permits and financial supports aimed at free drug administration.

During 2022, 22 MTB - IRE sessions were conducted during which 23 patients with common (e.g., lung, colorectal, breast cancer) or rare (e.g., sarcomas) cancers for which treatment options had ended were evaluated and discussed. In all cases, after a review of the clinical history and available genomic data, the MTB - IRE requested additional molecular testing, most often based on massive parallel sequencing. In some cases, immunohistochemistry analysis (e.g., PD-L1 status) and in situ hybridization (e.g., FGFR1 amplification or ROS1 fusion) were also required and applied. All collected data were integrated as orthogonal confirmatory measures and/or evaluated as stand-alone assays. Non-standard tests were supported by (and supplemented with) CE-IVD assays when possible. In 14 cases (61%), at least one peculiar molecular alteration associated with potential, additional tumor vulnerability was identified. Following review of MTB cases, nonstandard targeted therapy was recommended for 11 patients (48%).