Technological validation of the mir-THYpe® molecular testing platform: a suite of solutions based on microRNA profiling and mutation analysis for thyroid nodules

Abstract

Worldwide, there are two major problems in the management of patients with thyroid nodules: 1) High number of unnecessary thyroid surgeries. About 60% of the Brazilian population will identify a thyroid nodule at some point in their lives. Of the cases evaluated by biopsy (FNA - fine needle aspiration), between 20-30% will have an indeterminate result, not being possible, by current techniques, to differentiate the nodule between benign or malignant. The conduct in these cases is the Diagnostic Surgery, consisting of the removal of the thyroid gland to make the diagnosis of benignity or malignancy. However, between 70-80% of diagnostic thyroid surgeries reveal benign nodules, that is, they are unnecessary surgeries. 2) Necessary thyroid surgeries (cases of high probability of malignancy), but without sufficient information for personalization and planning. Malignant thyroid tumors are generally indolent and have a good prognosis. However, there are aggressive variants with a worse prognosis, which exhibit a high probability of recurrence, metastasis and even mortality. The pre-surgical lack of knowledge about the aggressiveness potential of a thyroid tumor prevents the best choice and customization of the surgical extension and urgency, generating cases of larger or smaller surgeries than ideal. It is important to emphasize that these are problems not only for patients, but are equally important for the sustainability of the health system (public and private). The target technological solution of this proposal is the mir-THYpe® molecular testing platform, which addresses specific solutions to the problems described above. As an alternative to diagnostic surgery for indeterminate nodules, we offer the mir-THYpe full exam. This solution analyzes a panel of microRNAs and, through a (proprietary) molecular classifier that uses artificial intelligence, classifies the indeterminate nodule as negative ("benign") or positive ("malignant") for malignancy. In addition, this exam analyzes the following prognostic markers: miR-375 expression and RET gene mutations, for identification of Medullary Carcinoma and selection of targeted therapy; expression of miR-146b and mutations in the BRAF and TERT genes, to predict a worse prognosis, aggressiveness and metastatic potential, risk of recurrence and mortality, helping to customize the surgical procedure when necessary. For the planning and customization of the necessary surgeries, the molecular prognostic markers mentioned above are offered in the two exams of the mir-THYpe® platform: full and pre-op, helping in the clinical and surgical decision on the customization of thyroid surgery. This proposed challenge has, therefore, the following objectives: A) To generate real-world data on the cost-effectiveness of the mir-THYpe® full exam in private supplementary health (health plans); B) Quantify and qualify the real impact on medical decision-making regarding the type and extent of surgery that will be performed based on prognostic molecular data (mir-THYpe full and pre-op) and the clinical outcomes of patients; C) Generate insights from the physician's experience in the use of mir-THYpe® platform exams. These objectives are mandatory to enable coverage of the mir-THYpe® platform by health plans (Rol ANS) and the public system (Conitec/SUS). In order to achieve these goals, we will offer exams from the mir-THYpe platform to our partner Hospital Samaritano (HS) in São Paulo, which is already on the list of the best hospitals in the world for the 3rd consecutive year. With this, we hope to overcome the challenges that, despite being part - and not the whole of the technological solution - will directly and decisively contribute not only to our understanding of their best use in the patient's journey and optimization of the use and experience of doctors in its use, but in the perception of the health system about how the mir-THYpe® platform can contribute to its sustainability. (AU)