**1. Introduction**

Tyrosine kinase inhibitors (TKIs) are a new class of oncological drugs with activity against receptors of different growth factors and able to inhibit pathways involved in tumor cell proliferation and neoangiogenesis [1]. They have been approved in many tumors including thyroid cancer as they play a crucial therapeutic role when conventional treatments are no longer effective [2]. To date, different TKIs have been approved by the Food and Drug Administration (FDA) and European Medical Agency (EMA) for RAI-refractory differentiated thyroid cancer (sorafenib and lenvatinib) and medullary

**Citation:** Dalmiglio, C.; Brilli, L.; Campanile, M.; Ciuoli, C.; Cartocci, A.; Castagna, M.G. CONUT Score: A New Tool for Predicting Prognosis in Patients with Advanced Thyroid Cancer Treated with TKI. *Cancers* **2022**, *14*, 724. https://doi.org/ 10.3390/cancers14030724

Academic Editor: Fabio Medas

Received: 13 December 2021 Accepted: 28 January 2022 Published: 30 January 2022

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thyroid cancer (vandetanib and cabozantinib), while dabrafenib/trametinib combination has obtained regulatory approval by the FDA for anaplastic thyroid cancer with a *BRAF* V600 mutation [3–7].

It has been demonstrated that TKIs significantly improved the progression free survival of patients with advanced disease; on the other hand, they are frequently associated with adverse events, which may affect the quality of life or request a permanent drug withdrawal in about 20% of cases [3–8]. TKIs are often associated with weight loss, anorexia, fatigue, and gastrointestinal side effects that may contribute to a malnutrition state.

Malnutrition is a common finding in cancer patients with advanced disease. It is associated with a reduction in physical function, it may negatively affect the prognosis and interfere with the anti-cancer treatment [9]. The energy deficit and the loss of lean body mass are related to the reduced food intake and metabolic disorders (increased basal metabolic rate, insulin-resistance, catabolic processes induced by cytokines and inflammatory factors), but anti-cancer therapy itself can also promote malnutrition.

Recent studies have shown the importance of single nutritional indices such as serum albumin in predicting poor outcomes in cancer patients [10–12]. Additionally, more complex indices have been developed and validated in order to evaluate the nutritional status [13,14]. The Controlling Nutritional Status (CONUT) score has recently been introduced as a nutritional screening tool [15]. Moreover, it has been recognized as a prognostic factor in patients affected by several chronic or malignant diseases [16–26].

Its utility has been demonstrated in the assessment of the prognosis of patients with end-stage liver disease and acute heart failure [16,17]; it has also been correlated with the disease activity in patients with lupus nephritis [27]. The impact of CONUT score on survival has also been reported in hospitalized elderly people [28] and in patients with hypertension [18] or in peritoneal dialysis [19]. Moreover, the prognostic role of CONUT score has been widely investigated in the context of several types of neoplasms. Many studies have demonstrated how a low CONUT score at the baseline correlates with a better prognosis in patients with small cell lung cancer, gastrointestinal, pancreatic, ovarian, breast, and urological cancers [20–26]. It has also been shown to be a parameter that correlates with prognosis and response to treatment in oncology [29].

To date, there are no studies in the literature that have investigated the relationship between CONUT score and thyroid cancer.

The aim of our study was to assess the CONUT score as a potential prognostic factor of response to therapy in patients with advanced thyroid cancer (differentiated, medullary, or poorly differentiated thyroid cancer) treated with TKIs.
