Browsing by Author "Vau, Nuno"

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    Immune Checkpoint Inhibitors for the Treatment of Bladder Cancer
    (MDPI, 2021-01-03) Lopez-Beltran, Antonio; Cimadamore, Alessia; Blanca, Ana; Massari, Francesco; Vau, Nuno; Scarpelli, Marina; Cheng, Liang; Montironi, Rodolfo; Pathology and Laboratory Medicine, School of Medicine
    A number of immune checkpoint inhibitors (ICIs) have been approved as first-line therapy in case of cisplatin-ineligible patients or as second-line therapy for patients with metastatic urothelial carcinoma (mUC) of the bladder. About 30% of patients with mUC will respond to ICIs immunotherapy. Programmed death-ligand 1 (PD-L1) expression detected by immunohistochemistry seems to predict response to immune checkpoint inhibitors in patients with mUC as supported by the objective response rate (ORR) and overall survival (OS) associated with the response observed in most clinical trials. Pembrolizumab, an anti-PD-1 antibody, demonstrated better OS respective to chemotherapy in a randomized phase 3 study for second-line treatment of mUC. Nivolumab, a PD-1 antibody, also demonstrated an OS benefit when compared to controls. Atezolizumab, Durvalumab, and Avelumab antibodies targeting PD-L1 have also received approval as second-line treatments for mUC with durable response for more than 1 year in selected patients. Atezolizumab and Pembrolizumab also received approval for first-line treatment of patients that are ineligible for cisplatin. A focus on the utility of ICIs in the adjuvant or neoadjuvant setting, or as combination with chemotherapy, is the basis of some ongoing trials. The identification of a clinically useful biomarker, single or in association, to determine the optimal ICIs treatment for patients with mUC is very much needed as emphasized by the current literature. In this review, we examined relevant clinical trial results with ICIs in patients with mUC alone or as part of drug combinations; emphasis is also placed on the adjuvant and neoadjuvant setting. The current landscape of selected biomarkers of response to ICIs including anti-PD-L1 immunohistochemistry is also briefly reviewed.
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    Predicting biochemical recurrence after radical prostatectomy: the role of prognostic grade group and index tumor nodule
    (Elsevier, 2019-11) Vau, Nuno; Henriques, Vanessa; Cheng, Liang; Blanca, Ana; Fonseca, Jorge; Montironi, Rodolfo; Cimadamore, Alessia; Lopez-Beltran, Antonio; Pathology and Laboratory Medicine, School of Medicine
    The aim of the current study was to test whether the grade group assessed in the index tumor nodule predicts biochemical recurrence after surgery. The study cohort series included 144 consecutive patients treated by laparoscopic radical prostatectomy. The following parameters were evaluated in each case: type of radical prostatectomy (with/without lymphadenectomy), pT and pN status, histologic type of prostate carcinoma (acinar versus mixed histology), surgical margin resection status, perineural invasion, lymphovascular invasion, biochemical recurrence status, presence of tertiary Gleason 5 pattern, and grade group that was assessed both in overall prostate cancer and in index (dominant) tumor nodule. Twenty patients (13.9%) experienced postoperative biochemical recurrence at a mean follow-up time of 12.2 months. The univariate survival analysis selected type of radical prostatectomy, histological subtype, lymphovascular invasion, American Joint Committee on Cancer pT and pN classification, tertiary Gleason 5 pattern, preoperative serum prostate specific antigen level, and the grade group assessed in both the overall prostate and index tumor nodule as significant for biochemical recurrence-free survival. Type of radical prostatectomy (P = .020), histological subtype (P = .002), lymphovascular invasion (P = .023), tertiary Gleason pattern 5 (P = .016), and grade group classification in index tumor nodule (P ≤ .0001) were selected as independent predictors of biochemical recurrence-free survival. In conclusion, our results validate grade group in the index tumor nodule as an independent predictor of biochemical recurrence-free survival, thus emphasizing the value of reporting grade group in index tumor nodule. The main limitation of our study is the relatively low number of cases in the current series, suggesting the need of large confirmatory studies.
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    Real-World Data on Cabozantinib in Previously Treated Patients with Metastatic Renal Cell Carcinoma: Focus on Sequences and Prognostic Factor
    (MDPI, 2019) Santoni, Matteo; Heng, Daniel Y.; Bracarda, Sergio; Procopio, Giuseppe; Milella, Michele; Porta, Camillo; Matrana, Marc R.; Cartenì, Giacomo; Crabb, Simon J.; De Giorgi, Ugo; Basso, Umberto; Masini, Cristina; Calabrò, Fabio; Vitale, Maria Giuseppa; Santini, Daniele; Massari, Francesco; Galli, Luca; Fornarini, Giuseppe; Ricotta, Riccardo; Buti, Sebastiano; Zucali, Paolo; Caffo, Orazio; Morelli, Franco; Carrozza, Francesco; Martignetti, Angelo; Gelibter, Alain; Iacovelli, Roberto; Mosca, Alessandra; Atzori, Francesco; Vau, Nuno; Incorvaia, Lorena; Ortega, Cinzia; Scarpelli, Marina; Lopez-Beltran, Antonio; Cheng, Liang; Paolucci, Vittorio; Graham, Jeffrey; Pierce, Erin; Scagliarini, Sarah; Sepe, Pierangela; Verzoni, Elena; Merler, Sara; Rizzo, Mimma; Sorgentoni, Giulia; Conti, Alessandro; Piva, Francesco; Cimadamore, Alessia; Montironi, Rodolfo; Battelli, Nicola; Pathology and Laboratory Medicine, School of Medicine
    Cabozantinib is approved for the treatment of renal cell carcinoma (RCC). However, prognostic factors are still lacking in this context. The aim of this study was to evaluate prognostic factors in RCC patients treated with second- or third-line cabozantinib. A multicenter retrospective real-world study was conducted, involving 32 worldwide centers. A total of 237 patients with histologically confirmed clear-cell and non-clear-cell RCC who received cabozantinib as second- or third-line therapy for metastatic disease were included. We analyzed overall survival (OS), progression-free survival (PFS) and time-to-strategy failure (TTSF) using Kaplan-Meier curves. Cox proportional models were used at univariate and multivariate analyses.The median PFS and OS of cabozantinib were 7.76 months (95% CI 6.51-10.88) and 11.57 months (95% CI 10.90-not reached (NR)) as second-line and 11.38 months (95% CI 5.79-NR) and NR (95% CI 11.51-NR) as third-line therapy. The median TTSF and OS were 11.57 and 15.52 months with the sequence of cabozantinib-nivolumab and 25.64 months and NR with nivolumab-cabozantinib, respectively. The difference between these two sequences was statistically significant only in good-risk patients. In the second-line setting, hemoglobin (Hb) levels (HR= 2.39; 95% CI 1.24-4.60, p = 0.009) and IMDC (International Metastatic Renal Cell Carcinoma Database Consortium) group (HR = 1.72, 95% CI 1.04-2.87, p = 0.037) were associated with PFS while ECOG-PS (HR = 2.33; 95%CI, 1.16-4.69, p = 0.018) and Hb levels (HR = 3.12; 95%CI 1.18-8.26, p = 0.023) correlated with OS at multivariate analysis, while in the third-line setting, only Hb levels (HR = 2.72; 95%CI 1.04-7.09, p = 0.042) were associated with OS. Results are limited by the retrospective nature of the study.This real-world study provides evidence on the presence of prognostic factors in RCC patients receiving cabozantinib.