Molecular Tumor Board as a Clinical Tool for Converting Molecular Data Into Real-World Patient Care.

PURPOSE: The investigation of multiple molecular targets with next-generation sequencing (NGS) has entered clinical practice in oncology, yielding to a paradigm shift from the histology-centric approach to the mutational model for personalized treatment. Accordingly, most of the drugs recently approved in oncology are coupled to specific biomarkers. One potential tool for implementing the mutational model of precision oncology in daily practice is represented by the Molecular Tumor Board (MTB), a multidisciplinary team whereby molecular pathologists, biologists, bioinformaticians, geneticists, medical oncologists, and pharmacists cooperate to generate, interpret, and match molecular data with personalized treatments. PATIENTS AND METHODS: Since May 2020, the institutional MTB set at Fondazione IRCCS Istituto Nazionale Tumori of Milan met weekly via teleconference to discuss molecular data and potential therapeutic options for patients with advanced/metastatic solid tumors. RESULTS: Up to October 2021, among 1,996 patients evaluated, we identified >10,000 variants, 43.2% of which were functionally relevant (pathogenic or likely pathogenic). On the basis of functionally relevant variants, 711 patients (35.6%) were potentially eligible to targeted therapy according to European Society of Medical Oncology Scale for Clinical Actionability of Molecular Targets tiers, and 9.4% received a personalized treatment. Overall, larger NGS panels (containing >50 genes) significantly outperformed small panels (up to 50 genes) in detecting actionable gene targets across different tumor types. CONCLUSION: Our real-world data provide evidence that MTB is a valuable tool for matching NGS data with targeted treatments, eventually implementing precision oncology in clinical practice.

Next generation diagnostic algorithm in non-small cell lung cancer predictive molecular pathology: The KWAY Italian multicenter cost evaluation study.

AIMS: The KWAY project aims to investigate the economic sustainability of the up-front NGS technologies adoption in the analysis of clinically relevant molecular alterations in NSCLC patients. METHODS: The diagnostic workflow and the related sustained costs of five Italian referral centers were assessed in four different evolving scenarios were analyzed. For each scenario, two alternative testing strategies were evaluated: the Maximized Standard strategy and the Maximized NGS strategy. RESULTS: For each center, the robustness of obtained results was verified through a deterministic sensitivity analysis, observing the variation of total costs based on a variation of ±20 % of the input parameters and ensuring that results would present a consistent behavior compared to the original ones. CONCLUSIONS: our project, highlighted that the adoption of NGS allows to save personnel time dedicated to testing activities and to reduce the overall cost of testing per patient.

Next-Generation Sequencing in Clinical Practice: Is It a Cost-Saving Alternative to a Single-Gene Testing Approach?

OBJECTIVES: This study aimed to compare the costs of a next-generation sequencing-based (NGS-based) panel testing strategy to those of a single-gene testing-based (SGT-based) strategy, considering different scenarios of clinical practice evolution. METHODS: Three Italian hospitals were analysed, and four different testing pathways (paths 1, 2, 3, and 4) were identified: two for advanced non-small-cell lung cancer (aNSCLC) patients and two for unresectable metastatic colon-rectal cancer (mCRC) patients. For each path, we explored four scenarios considering the current clinical practice and its expected evolution. The 16 testing cases (4 scenarios × 4 paths) were then compared in terms of differential costs between the NGS-based and SGT-based approaches considering personnel, consumables, equipment, and overhead costs. Break-even and sensitivity analyses were performed. Data gathering, aimed at identifying the hospital setup, was performed through a semi-structured questionnaire administered to the professionals involved in testing activities. RESULTS: The NGS-based strategy was found to be a cost-saving alternative to the SGT-based strategy in 15 of the 16 testing cases. The break-even threshold, the minimum number of patients required to make the NGS-based approach less costly than the SGT-based approach, varied across the testing cases depending on molecular alterations tested, techniques adopted, and specific costs. The analysis found the NGS-based approach to be less costly than the SGT-based approach in nine of the 16 testing cases at any volume of tests performed; in six cases, the NGS-based approach was found to be less costly above a threshold (and in one case, it was found to be always more expensive). Savings obtained using an NGS-based approach ranged from €30 to €1249 per patient; in the unique testing case where NGS was more costly, the additional cost per patient was €25. CONCLUSIONS: An NGS-based approach may be less costly than an SGT-based approach; also, generated savings increase with the number of patients and different molecular alterations tested.