Browsing by Author "Schiavina, Riccardo"

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    Current Strategies and Novel Therapeutic Approaches for Metastatic Urothelial Carcinoma
    (MDPI, 2020-06-02) Mollica, Veronica; Rizzo, Alessandro; Montironi, Rodolfo; Cheng, Liang; Giunchi, Francesca; Schiavina, Riccardo; Santoni, Matteo; Fiorentino, Michelangelo; Lopez-Beltran, Antonio; Brunocilla, Eugenio; Brandi, Giovanni; Massari, Francesco; Pathology and Laboratory Medicine, School of Medicine
    Urothelial carcinoma (UC) is a frequent cause of cancer-related deaths worldwide. Metastatic UC has been historically associated with poor prognosis, with a median overall survival of approximately 15 months and a 5-year survival rate of 18%. Although platinum-based chemotherapy remains the mainstay of medical treatment for patients with metastatic UC, chemotherapy clinical trials produced modest benefit with short-lived, disappointing responses. In recent years, the better understanding of the role of immune system in cancer control has led to the development and approval of several immunotherapeutic approaches in UC therapy, where immune checkpoint inhibitors have been revolutionizing the treatment of metastatic UC. Because of a better tumor molecular profiling, FGFR inhibitors, PARP inhibitors, anti-HER2 agents, and antibody drug conjugates targeting Nectin-4 are also emerging as new therapeutic options. Moreover, a wide number of trials is ongoing with the aim to evaluate several other alterations and pathways as new potential targets in metastatic UC. In this review, we will discuss the recent advances and highlight future directions of the medical treatment of UC, with a particular focus on recently published data and ongoing active and recruiting trials.
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    Evaluation of an institutional series of low-grade oncocytic tumor (LOT) of the kidney and review of the mutational landscape of LOT
    (Springer, 2023) Ricci, Costantino; Ambrosi, Francesca; Franceschini, Tania; Giunchi, Francesca; Grillini, Alessia; Franchini, Eugenia; Grillini, Marco; Schiavina, Riccardo; Massari, Francesco; Mollica, Veronica; Tateo, Valentina; Bianchi, Federico Mineo; Bianchi, Lorenzo; Droghetti, Matteo; Maloberti, Thais; Tallini, Giovanni; Colecchia, Maurizio; Acosta, Andres Martin; Lobo, João; Trpkov, Kiril; Fiorentino, Michelangelo; de Biase, Dario; Pathology and Laboratory Medicine, School of Medicine
    The 2022 WHO classification of urinary and male genital tumors introduced several novel kidney entities exhibiting eosinophilic/oncocytic features with specific mutational backgrounds. Thus, molecular techniques, such as next-generation sequencing (NGS), became more commonly used for their evaluation. We studied 12 low-grade oncocytic tumors (LOT) of the kidney (from 11 patients), identified in a cohort of 210 eosinophilic/oncocytic renal tumors, diagnosed in our institution between October 2019 and May 2023, which represented 5.7% (12/210) of all eosinophilic/oncocytic renal tumors during this period. We reviewed their clinicopathologic, histologic, and immunohistochemical features, as well as their mutational profiles. We also reviewed the literature on NGS-derived data of LOT, by selecting papers in which LOT diagnosis was rendered according to the criteria proposed initially. Median age was 65 years (mean: 63.5; range 43–79) and median tumor size was 2.0 cm (mean: 2.2; range: 0.9–3.1). All tumors were positive for PAX8, CK7, and GATA3, and negative or focally positive for CD117/KIT. We found the following gene mutations: MTOR ((6/11), 54.5%)), TSC1 ((2/11), 18.2%)), and 1 had both NOTCH1 and NOTCH4 ((1/11), 9.1%)). Wild-type status was found in 2/11 (18.2%) patients and one tumor was not analyzable. A review of 8 previous studies that included 79 LOTs revealed frequent mutations in the genes that regulate the mammalian target of rapamycin (mTOR) pathway: MTOR (32/79 (40.5%)), TSC1 (21/79 (26.6%)), and TSC2 (9/79 (11.4%)). Other mutated genes included PIK3CA, NF2, and PTEN, not typically known to affect the mTOR pathway, but potentially acting as upstream and downstream effectors. Our study shows that LOT is increasingly diagnosed in routine practice when applying the appropriate diagnostic criteria. We also confirm that the mTOR pathway is strongly implicated in the pathogenesis of this tumor mainly through MTOR, TCS1, and TSC2 mutations, but other genes could also be involved in the pathway activation, especially in LOTs without “canonical” mutations.
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    TNM staging towards a personalized approach in metastatic urothelial carcinoma: what will the future be like?—a narrative review
    (AME Publishing, 2021-03) Rizzo, Alessandro; Mollica, Veronica; Cimadamore, Alessia; Santoni, Matteo; Scarpelli, Marina; Schiavina, Riccardo; Cheng, Liang; Lopez-Beltran, Antonio; Brunocilla, Eugenio; Montironi, Rodolfo; Massari, Francesco; Pathology and Laboratory Medicine, School of Medicine
    The American Joint Committee of Cancer (AJCC) tumor-node-metastasis (TNM) classification, with its periodical updates and modifications, has represented and still represents the basis of cancer staging. The historical, long-standing limitations of anatomic-based TNM staging have been recently “threatened” by the impressive amount of data derived from molecular analyses, which have led to an unprecedented level of understanding of cancer genomics. In fact, current era of personalized oncology has witnessed important efforts towards the integration between clinical, anatomical and molecular features; however, despite the promises, personalized oncology faces many obstacles, due to the complex relationship between tumor biomarkers, previously unknown cancer subtypes and clinical and anatomical characteristics. With regard to urothelial carcinoma (UC), the characterization of tumors in large cohorts of patients has provided important information concerning genetic alterations, revealing the presence of biologically relevant subtypes of UC. In the current review, we will provide an overview regarding this recent “translation” from the anatomic-based TNM to a novel horizon, aiming at further “tailoring” personalized oncology, especially focusing on recently published data about the molecular landscape of UC with its therapeutic and prognostic implications.