Molecular tumour board in gastrointestinal cancers

Abstract

Background: Comprehensive genomic profiling (CGP) is being increasingly adopted in clinical practice to guide the use of molecularly guided treatment options (MGTOs). To optimize the integration of MGTOs in routine cancer care, molecular tumour boards (MTBs) have been established. Limited data are available to address the clinical value of implementing MTBs to inform treatment decision making in patients with gastrointestinal (GI) cancers.

Materials and methods: We retrospectively retrieved medical records from patients with advanced GI cancers discussed at the European Institute of Oncology's MTB between August 2019 and December 2024. We evaluated clinical outcomes resulting from applying MGTOs in cancer care according to MTB recommendations, describing real-world progression-free (rwPFS) and overall survival (OS), and used the growth modulation index (GMI) (ratio of PFS^MTB to PFS^prior) to quantify the effectiveness of MTB's recommended cancer treatment in extending PFS.

Results: Among 192 patients with GI cancers discussed at MTB, 139 (72.3%) received an MTB treatment recommendation. For patients with available follow-up data (n = 82), 31 patients (41.4%, 17.7% overall) received MGTOs, while 51 patients received standard treatments. Patients receiving MGTOs exhibited a longer rwPFS compared with cases receiving standard therapies [5.35 versus 3.55 months, hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.36-1.08, P = 0.08] and with unmatched cases showing actionable biomarkers but not treated with targeted agents (n = 31) (rwPFS 5.35 versus 2.40 months, HR 0.49, 95% CI 0.27-0.90, P = 0.02). The use of MGTOs resulted in a GMI of 1.12 (interquartile range 0.68-2.36). The European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of molecular Targets (ESCAT) tier I-III treatments resulted in a restricted mean PFS gain of 4.87 months compared with standard therapies (95% CI 1.02-8.72 months, P = 0.01). No OS difference was observed between patients receiving MGTOs and standard treatments (P = 0.89).

Conclusions: Our results suggest that MTB-informed clinical decision making could provide valuable clinical benefits and expanded therapeutic options in patients affected by advanced GI cancers.

Keywords: gastrointestinal cancers; genomic profiling; molecular tumour board; next-generation sequencing; precision medicine; target therapy.

Figure 1

Study flowchart and patients characteristics. (A) Study flowchart of patients affected by gastrointestinal tumours discussed at the MTB. (B) Type of primary tumours discussed at the MTB. (C) Oncoprint of discussed cases, showing top 20 mutated genes with primary tumour site and receipt of treatment recommendations annotated on top. (D) Proportion of cases receiving an MTB recommendation stratified for type of primary tumour. BTC, biliary tract cancer; CRC, colorectal cancer; Indel, insertion–deletion; MTB, molecular tumour board.

Figure 2

Clinical outcomes for patients receiving MTB’s treatment recommendations. (A) Real-world PFS of cases receiving MGTOs and standard treatment. (B) Real-world PFS between cases receiving MGTOs and standard treatment, with the former stratified for those showcasing actionable biomarkers which received an MTB treatment recommendation (unmatched) and those without actionable biomarkers (non-actionable). (C) Swimmer plot of real-world PFS on MGTOs compared with the previous line of standard treatment, with MGTOs’ targets displayed on the left annotation and the label ‘X’ showing patients with a PFS event at the last follow-up. CI, confidence interval; ERBB2, Erb-B2 receptor tyrosine kinase 2; FGFR2, fibroblast growth factor receptor 2; IDH1, isocitrate dehydrogenase 1; MGTO, molecularly guided treatment option; MSI-H, microsatellite instability high; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; PFS, progression-free survival; PTEN, PTEN-phosphatase and tensin homolog; TMB-H, tumor mutational burden high.

Figure 3

Clinical and molecular determinants of MGTOs benefit. (A) Real-world PFS according to ESCAT tiers among patients treated with MGTOs. (B) Oncoprint of patients treated with MGTOs and which received a wide comprehensive genomic profiling panel included in the clinicogenomic analysis, with PFS time on top and clinical annotation on bottom of the Oncoprint. (C) SHAP values of top 10 features associated with or without clinical benefit from MGTOs arranged in decreasing order; values on the left associate with a lack of clinical benefit from MGTOs, while values on the right associate with clinical benefit from MGTOs. ADC, antibody–drug conjugates; BOR, best overall response; Indel, insertion–deletion; IO, immuno-oncology agents; mAb, monoclonal antibody; MGTO, molecularly guided treatment option; mut, mutated; PFS, progression-free survival; SHAP, SHapley Additive exPlanations; SNV, single nucleotide variant; TKI, tyrosine kinase inhibitors; wt, wild type.