The molecular tumor board as a step in cancer patient management: a southern Italian experience

Abstract

Introduction: The management of cancer patients follows a Diagnostic Therapeutic and Care Pathway (PDTA) approach, aimed at achieving the optimal balance between care and quality of life. To support this process, precision medicine and innovative technologies [e.g., next-generation sequencing (NGS)] allow rapid identification of genetic-molecular alterations useful for the design of PDTA-approved therapies. If the standard approach proves inadequate, the Molecular Tumor Board (MTB), a group comprising specialists from diverse disciplines, can step in to evaluate a broader molecular profile, proposing potential therapies beyond evidence levels I-II or considering enrolment in clinical trials. Our aim is to analyze the role of the MTB in the entire management of patients in our institute and its impact on the strategy of personalized medicine, particularly when all approved treatments have failed.

Materials and methods: In alignment with European and national guidelines, a panel of clinicians and preclinical specialists from our institution was defined as the MTB core team. We designed and approved a procedure for the operation of this multidisciplinary group, which is the only one operating in the Puglia region.

Results and discussion: In 29 months (2021-2023), we discussed and analyzed 93 patients. A total of 44% presented pathogenic alterations, of which 40.4% were potentially actionable. Only 11 patients were proposed for enrollment in clinical trials, treatment with off-label drugs, or AIFA (the Italian pharmaceutical agency for drugs)-5% funding. Our process indicators, time to analysis, and number of patient cases discussed are in line with the median data of other European institutions. Such findings underscore both the importance and usefulness of the integration of an MTB process into the care of oncology patients.

Keywords: Molecular Tumor Board; comprehensive genomic profile; liquid biopsy; precision medicine; team.

Figure 1

MTB workflow. The figure emphasizes that the patient is discussed in the MTB by a clinician after the decision of the Multidisciplinary Pathology Team (MTP). A data manager provides the patient ID and initiates the analysis in-house or by outsourcing. The molecular biologists perform the analysis and call up the variants annotated by the bioinformatician. All data are discussed again in the MTB and the possibility of treatment is discussed (off-label, Italian trials, AIFA funds, etc.). After discussion, the report is sent back to the clinician.

Figure 2

Decisional tree from patient discussion to eventual treatment. MTB, molecular tumor board; PDTA, diagnostic therapeutic and care pathway; MTP, multidisciplinary team of pathology; CGP, comprehensive genomic profile.

Figure 3

Pathologies discussed in MTB, are common and rare. Leiomyosarcoma (LMS); colon adenocarcinoma (CRC); breast carcinoma (BC); lung adenocarcinoma (L-ADC); pancreatic adenocarcinoma (P-ADC); cholangiocarcinoma (CCA); salivary adenocarcinoma (S-ADC); melanoma (SSM); ovarian carcinoma (OC); pheochromocytoma (PCC); poorly differentiated enteric-type carcinoma (pdEC); splenic angiosarcoma (PSA); angiosarcoma/hepatic carcinoma (PHA); gastric carcinoma (GC); endometrial carcinoma (EC); anal squamous cell carcinoma (SCCA); dedifferentiated liposarcoma (DDLPS); testicular carcinoma (TC); biliary tract carcinoma (BTC); hepatic carcinoma (HC); gliosarcoma (GS); desmoplastic small-round-cell carcinoma (DSRCT); squamous cell carcinoma in the cervical lymph nodes (SCC-CL); anaplastic astrocytoma (ANA); yolk sac tumor (YST); bone metastasis of carcinoma with sarcomatoid features (sBMC); myxoid liposarcoma (MLPS); atypical meningioma (AM); poorly differentiated mucinous carcinoma of gastrointestinal origin (MGC); clivus chordoma (CC); sarcoid myxofibrosarcoma (sMFS); pleomorphic rhabdomyosarcoma (PRMS); granulosa cell cancer (GCT); and atypical teratoid rhabdoid tumor (ATRT).

Figure 4

Oncoprint depicting alterations annotated in the tissue of patients where cases with no relevant alterations were excluded has been displayed (A). Oncoprint depicting alterations annotated in the plasma of patients where cases with no relevant alterations were excluded has been displayed (B). The numbers shown in the figure are the times when an alteration in a given gene was present.