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Giuseppe PUGLIESE

Assegnista di ricerca
Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto

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Pubblicazioni

2022 - Myocarditis and diaphragmatic rhabdomyolysis with respiratory failure in a patient with metastatic melanoma treated with Nivolumab [Articolo su rivista]
Baldessari, C.; Pugliese, G.; Venturelli, M.; Greco, S.; Ferrara, L.; Longo, G.; Dominici, M.; Depenni, R.
abstract

Introduction: Immunotherapy dramatically changed history of melanoma patients with a clinical benefit never seen before. Nevertheless, severe and unexpected adverse effects can occur, fortunately rarely. Case presentation: We reported the case of a 75-year-old male patient affected by metastatic melanoma who developed myocarditis and acute rhabdomyolysis with secondary diaphragmatic dysfunction and consequent pulmonary restrictive syndrome after Nivolumab monotherapy. Blood tests and ultrasonography of the diaphragm revealing left hypokinesis suggested a Nivolumab-related rhabdomyolysis, as an immune-mediated adverse event. The rhabdomylolysis involved the diaphragm with consequent diaphragmatic weakness and respiratory distress. Mangement & outcome: The patient had a slow but slight and progressive improvement of symptoms and vital signs post-treatment with high-dose corticosteroids. Discussion: With this case report, we want to highlight the importance of rapid recognition and treatment of rare and unexpected, but potential serious immune-related adverse events. These events might happen despite the remarkable clinical benefits of immune checkpoint inhibitors. We do not know which patients will benefit from these therapies and why, when and in which cases adverse event will occur: we must not lower our attention.

2021 - Body composition and inflammation impact in non-small cell lung cancer patients treated by first-line immunotherapy [Articolo su rivista]
Baldessari, Cinzia; Pecchi, Annarita; Marcheselli, Raffaella; Guaitoli, Giorgia; Bonacini, Riccardo; Valoriani, Filippo; Torricelli, Pietro; Reverberi, Linda; Menozzi, Renata; Pugliese, Giuseppe; Vitale, Maria Giuseppa; Sabbatini, Roberto; Bertolini, Federica; Barbieri, Fausto; Dominici, Massimo
abstract

Lay abstract Inflammation and malnutrition in cancer patients may affect the immune system and response to therapy. We noticed an increase in inflammation and visceral fat and a decrease in muscle and subcutaneous fat during therapy. No variation showed a significant correlation with survival. Muscle mass, adipose tissue and body mass index do not confirm any prognostic impact or relationship with response to therapy. More interesting results were observed with parameters related to inflammation. Probably, for the best treatment choice, a combination of clinical and biological factors will be necessary. Further studies with a multidimensional approach are needed to propose the best treatment and the best support to everyone.Tweetable abstract Body composition, nutritional and inflammatory status changed during first-line immunotherapy on NSCLC patients. Inflammation has interesting prognostic implications. Combined with other factors, these clinical characteristics may be important to optimize the care of patients.Background: Immunotherapy changed the landscape of non-small cell lung cancer (NSCLC). Efforts were made to implement its action. This study aims to describe body composition, nutritional and inflammatory status in NSCLC patients treated by first-line immunotherapy, their correlation, variation and impact. Patients and methods: We retrospectively analyzed 44 consecutive patients who received pembrolizumab treatment. Results: During the therapy, inflammation and visceral fat increased, whereas muscle and subcutaneous fat decreased. Parameters related to inflammation had an interesting prognostic impact. High numbers of white blood cells remained significantly correlated with a high risk of death in multivariate model. Conclusion: For the best treatment choice, a combination of clinical and biological factors will be most likely be necessary. Prospective and larger studies with a multidimensional approach are needed.

2021 - Cemiplimab- and nivolumab-induced myasthenia gravis: two clinical cases [Articolo su rivista]
Canino, F.; Pugliese, G.; Baldessari, C.; Greco, S.; Depenni, R.; Dominici, M.
abstract

Immune-related myasthenia gravis is a rare, disabling, and potentially fatal adverse event of immune checkpoint inhibitor treatment. It is important to identify and manage it promptly. We present two cases of immune-related de novo myasthenia gravis observed at the Modena Cancer Center in two elderly patients treated with two anti-PD-1 monoclonal antibodies: cemiplimab and nivolumab.

2020 - Improving the international prognostic index score using peripheral blood counts: Results of a large multicenter study involving 520 patients with diffuse large B cell lymphoma [Articolo su rivista]
Marcheselli, Raffaella; Bari, Alessia; Tadmor, Tamar; Marcheselli, Luigi; Cox, Maria Christina; Papotti, Robel; Ferrari, Angela; Baldini, Luca; Gobbi, Paolo; Levy, Ilana; Pugliese, Giuseppe; Federico, Massimo; Polliack, Aaron; Pozzi, Samantha; Sacchi, Stefano
abstract

The main purpose of this study was to assess whether it is possible to improve the prognostic impact of international prognostic index (IPI) score by combining it with peripheral blood counts. Thus, we evaluated the prognostic power of lymphocyte, neutrophil, and monocyte counts in 520 patients with diffuse large B cell lymphoma treated with R-CHOP, confirming that these parameters have a strong impact on overall survival (OS). Using revised IPI (R-IPI), 44% of patients were categorized as poor-risk and showed an OS at 5 years of 46%. As OS at 5 years of the 520 patients is 67%, it is clearly evident that R-IPI tends to overestimate the proportion of patients with poor prognosis. Accordingly, in an attempt to improve the discriminating power of R-IPI, we evaluated and compared three different scores by combining the neutrophil lymphocyte ratio (NLR) and absolute monocyte count (AMC) with the following values: (a) IPI score 3-5, (b) age > 60 years and performance status, (c) age >= 65 years and LDH > ULN. The three indexes studied, had a similar 5 years OS for the high-risk group (46%-52%), but the proportion of patients classified as poor-risk were 37%, 20%, and 32%, respectively, which are lower than 44% identified with R-IPI. Thus, while R-IPI overestimates the number of high-risk patients, after applying our models, it is possible to recognize patients who are truly at high-risk. Of the three scores, the most accurate appears to be that based on NLR, AMC, LDH > ULN and age >= 65 years, which identifies 32% of high-risk patients, correlating well with what is seen in clinical practice.

2019 - Immune inflammation indicators in anal cancer patients treated with concurrent chemoradiation: training and validation cohort with online calculator (ARC: Anal Cancer Response Classifier) [Articolo su rivista]
Casadei-Gardini, Andrea; Montagnani, Francesco; Casadei, Chiara; Arcadipane, Francesca; Andrikou, Kalliopi; Aloi, Deborah; Prete, Alessandra Anna; Zampino, Maria Giulia; Argentiero, Antonella; Pugliese, Giuseppe; Martini, Stefania; Iorio, Giuseppe Carlo; Scartozzi, Mario; Mistrangelo, Massimiliano; Fornaro, Lorenzo; Cassoni, Paola; Marisi, Giorgia; Dell'Acqua, Veronica; Ravenda, Paola Simona; Lonardi, Sara; Silvestris, Nicola; De Bari, Berardino; Ricardi, Umberto; Cascinu, Stefano; Franco, Pierfrancesco
abstract

Background: In anal cancer, there are no markers nor other laboratory indexes that can predict prognosis and guide clinical practice for patients treated with concurrent chemoradiation. In this study, we retrospectively investigated the influence of immune inflammation indicators on treatment outcome of anal cancer patients undergoing concurrent chemoradiotherapy. Methods: All patients had a histologically proven diagnosis of squamous cell carcinoma of the anal canal/margin treated with chemoradiotherapy according to the Nigro's regimen. Impact on prognosis of pre-treatment systemic index of inflammation (SII) (platelet x neutrophil/lymphocyte), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were analyzed. Results: A total of 161 consecutive patients were available for the analysis. Response to treatment was the single most important factor for progression-free survival (PFS) and overall survival (OS). At univariate analysis, higher SII level was significantly correlated to lower PFS (p<0.01) and OS (p=0.046). NLR level was significantly correlated to PFS (p=0.05), but not to OS (p=0.06). PLR level significantly affected both PFS (p<0.01) and OS (p=0.02). On multivariate analysis pre-treatment, SII level was significantly correlated to PFS (p=0.0079), but not to OS (p=0.15). We developed and externally validated on a cohort of 147 patients a logistic nomogram using SII, nodal status and pre-treatment Hb levels. Results showed a good predictive ability with C-index of 0.74. An online available calculator has also been developed. Conclusion: The low cost and easy profile in terms of determination and reproducibility make SII a promising tool for prognostic assessment in this oncological setting.

2017 - Neutrophil-lymphocyte ratio at diagnosis is an independent prognostic factor in patients with nodular sclerosis Hodgkin lymphoma: Results of a large multicenter study involving 990 patients [Articolo su rivista]
Marcheselli, Raffaella; Bari, Alessia; Tadmor, Tamar; Marcheselli, Luigi; Cox, Maria Christina; Pozzi, Samantha; Ferrari, Angela; Baldini, Luca; Gobbi, Paolo; Aviv, Ariel; Pugliese, Giuseppe; Federico, Massimo; Polliack, Aaron; Sacchi, Stefano
abstract

Several studies have demonstrated the prognostic value of neutrophil-lymphocyte ratio (NLR) in patients with solid tumors and non-Hodgkin lymphoma. In contrast, there is only sparse data on its prognostic role in patients with classical Hodgkin lymphoma (cHL). The aim of our study was to establish whether NLR could serve as an independent prognostic factor in a cohort of 990 patients with nodular sclerosis (NS)-cHL. After analysis of the log hazard ratio (HR) as a function of NLR, we chose the value 6 as cutoff. Patients with NLR >6 had a worse progression-free survival and overall survival compared to those with NLR ≤6; 84% vs 75% and 92% vs 88%, at 5 years, with an HR of 1.65 and 1.82, respectively. Multivariate analysis showed that the risk remained high with HR 1.44 and HR 1.54 in progression-free survival and overall survival, respectively. In summary, our study shows that NLR is a robust and independent prognostic parameter in NS-cHL, both in early and advanced disease. It is inexpensive and simple to apply. Thus, we conclude that NLR, possibly in combination with the international prognostic score and absolute monocyte count, is a useful guide for physicians treating NS-cHL patients.

2016 - The evolving role of microsatellite instability in colorectal cancer: A review [Articolo su rivista]
Gelsomino, Fabio; Barbolini, Monica; Spallanzani, Andrea; Pugliese, Giuseppe; Cascinu, Stefano
abstract

Microsatellite instability (MSI) is a molecular marker of a deficient mismatch repair (MMR) system and occurs in approximately 15% of colorectal cancers (CRCs), more frequently in early than late-stage of disease. While in sporadic cases (about two-thirds of MSI-H CRCs) MMR deficiency is caused by an epigenetic inactivation of MLH1 gene, the remainder are associated with Lynch syndrome, that is linked to a germ-line mutation of one of the MMR genes (MLH1, MSH2, MSH6, PMS2). MSI-H colorectal cancers have distinct clinical and pathological features such as proximal location, early-stage (predominantly stage II), poor differentiation, mucinous histology and association with BRAF mutations. In early-stage CRC, MSI can select a group of tumors with a better prognosis, while in metastatic disease it seems to confer a negative prognosis. Although with conflicting results, a large amount of preclinical and clinical evidence suggests a possible resistance to 5-FU in these tumors. The higher mutational load in MSI-H CRC can elicit an endogenous immune anti-tumor response, counterbalanced by the expression of immune inhibitory signals, such as PD-1 or PD-L1, that resist tumor elimination. Based on these considerations, MSI-H CRCs seem to be particularly responsive to immunotherapy, such as anti-PD-1, opening a new era in the treatment landscape for patients with metastatic CRC.