324 results on '"Napoli"'
Search Results
2. Adequacy of Pain Management in Patients Referred for Radiation Therapy: A Subanalysis of the Multicenter ARISE-1 Study
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Donati, Costanza M., primary, Maggiore, Chiara Maria, additional, Maltoni, Marco, additional, Rossi, Romina, additional, Nardi, Elena, additional, Zamagni, Alice, additional, Siepe, Giambattista, additional, Mammini, Filippo, additional, Cellini, Francesco, additional, Di Rito, Alessia, additional, Portaluri, Maurizio, additional, De Tommaso, Cristina, additional, Santacaterina, Anna, additional, Tamburella, Consuelo, additional, Di Franco, Rossella, additional, Parisi, Salvatore, additional, Cossa, Sabrina, additional, Fusco, Vincenzo, additional, Bianculli, Antonella, additional, Ziccarelli, Pierpaolo, additional, Ziccarelli, Luigi, additional, Genovesi, Domenico, additional, Caravatta, Luciana, additional, Deodato, Francesco, additional, Macchia, Gabriella, additional, Fiorica, Francesco, additional, Napoli, Giuseppe, additional, Buwenge, Milly, additional, and Morganti, Alessio G., additional
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- 2023
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3. Exploring the Potential of Non-Coding RNAs as Liquid Biopsy Biomarkers for Lung Cancer Screening: A Literature Review
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Garbo, Edoardo, primary, Del Rio, Benedetta, additional, Ferrari, Giorgia, additional, Cani, Massimiliano, additional, Napoli, Valerio Maria, additional, Bertaglia, Valentina, additional, Capelletto, Enrica, additional, Rolfo, Christian, additional, Novello, Silvia, additional, and Passiglia, Francesco, additional
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- 2023
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4. Serum Paraprotein Is Associated with Adverse Prognostic Factors and Outcome, across Different Subtypes of Mature B-Cell Malignancies—A Systematic Review
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Cox, Maria Christina, primary, Esposito, Fabiana, additional, Postorino, Massimiliano, additional, Venditti, Adriano, additional, and Di Napoli, Arianna, additional
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- 2023
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5. DICER1 Syndrome: A Multicenter Surgical Experience and Systematic Review
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Spinelli, Claudio, primary, Ghionzoli, Marco, additional, Sahli, Linda Idrissi, additional, Guglielmo, Carla, additional, Frascella, Silvia, additional, Romano, Silvia, additional, Ferrari, Carlo, additional, Gennari, Fabrizio, additional, Conzo, Giovanni, additional, Morganti, Riccardo, additional, De Napoli, Luigi, additional, Quaglietta, Lucia, additional, De Martino, Lucia, additional, Picariello, Stefania, additional, Grandone, Anna, additional, Luongo, Caterina, additional, Gambale, Antonella, additional, Patrizio, Armando, additional, Fallahi, Poupak, additional, Antonelli, Alessandro, additional, and Ferrari, Silvia Martina, additional
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- 2023
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6. Genetic Ablation of the MET Oncogene Defines a Crucial Role of the HGF/MET Axis in Cell-Autonomous Functions Driving Tumor Dissemination
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Modica, Chiara, primary, Cortese, Marco, additional, Bersani, Francesca, additional, Lombardi, Andrea Maria, additional, Napoli, Francesca, additional, Righi, Luisella, additional, Taulli, Riccardo, additional, Basilico, Cristina, additional, and Vigna, Elisa, additional
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- 2023
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7. Analysis of Health-Related Quality of Life Reporting in Phase III RCTs of Advanced Genitourinary Tumors.
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Di Costanzo, Fabrizio, Napolitano, Fabiana, Salomone, Fabio, Amato, Anna Rita, Alberico, Gennaro, Migliaccio, Fortuna, Pecoraro, Giovanna, Marra, Annachiara, Crocetto, Felice, Ruffo, Antonio, Scagliarini, Sarah, Rossetti, Sabrina, Puglia, Livio, Di Napoli, Marilena, Bianco, Roberto, Servetto, Alberto, and Formisano, Luigi
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ONLINE information services ,GENITOURINARY organ tumors ,SYSTEMATIC reviews ,HEALTH status indicators ,TUMOR classification ,QUALITY of life ,DESCRIPTIVE statistics ,RESEARCH funding ,MEDLINE - Abstract
Simple Summary: In this manuscript, we investigate the reporting rate of health-related quality of life (HRQoL) in phase III RCTs evaluating therapies in advanced genitourinary cancers published between 2010 and 2022. Results showed underreporting of HRQoL and the need to dedicate more attention to its assessment. Background: As recommended in the European Society for Medical Oncology (ESMO) guidelines, assessment of health-related quality of life (HRQoL) should be a relevant endpoint in randomized controlled trials (RCTs) testing new anticancer therapies. However, previous publications by our group and others revealed a frequent underestimation and underreporting of HRQoL results in publication of RCTs in oncology. Herein, we systematically reviewed HRQoL reporting in RCTs testing new treatments in advanced prostate, kidney and urothelial cancers and published between 2010 and 2022. Methods: We searched PubMed RCTs testing novel therapies in genitourinary (GU) cancers and published in fifteen selected journals (Annals of Oncology, BMC Cancer, British Journal of Cancer, Cancer Discovery, Clinical Cancer Research, Clinical Genitourinary cancer, European Journal of Cancer, European Urology, European Urology Oncology, JAMA, JAMA Oncology, Journal of clinical Oncology, Lancet, Lancet Oncology and The New England Journal of Medicine). We excluded trials investigating exclusively best supportive care or behavioral intervention, as well as subgroup or post hoc analyses of previously published trials. For each RCT, we investigated whether HRQoL assessment was performed by protocol and if results were reported in the primary manuscript or in a secondary publication. Results: We found 85 eligible trials published between 2010 and 2022. Only 1/85 RCTs (1.2%) included HRQoL among primary endpoints. Of note, 25/85 (29.4%) RCTs did not include HRQoL among study endpoints. HRQoL results were non-disclosed in 56/85 (65.9%) primary publications. Only 18/85 (21.2%) publications fulfilled at least one item of the CONSORT-PRO checklist. Furthermore, 14/46 (30.4%) RCTs in prostate cancer, 12/25 (48%) in kidney cancer and 3/14 (21.4%) in urothelial cancer reported HRQoL data in primary publications. Next, HRQoL data were disclosed in primary manuscripts of 12/32 (37.5%), 5/13 (38.5%), 5/16 (31.3%) and 5/15 (33.3%) trials evaluating target therapies, chemotherapy, immunotherapy and new hormonal agents, respectively. Next, we found that HRQoL data were reported in 16/42 (38%) and in 13/43 (30.2%) positive and negative trials, respectively. Finally, the rate of RCTs reporting HRQoL results in primary or secondary publications was 55.3% (n = 47/85). Conclusions: Our analysis revealed a relevant underreporting of HRQoL in RCTs in advanced GU cancers. These results highlight the need to dedicate more attention to HRQoL in RCTs to fully assess the value of new anticancer treatments. [ABSTRACT FROM AUTHOR]
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- 2023
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8. Cardiotoxicity, Cardioprotection, and Prognosis in Survivors of Anticancer Treatment Undergoing Cardiac Surgery: Unmet Needs
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Palmieri, Vittorio, primary, Vietri, Maria Teresa, additional, Montalto, Andrea, additional, Montisci, Andrea, additional, Donatelli, Francesco, additional, Coscioni, Enrico, additional, and Napoli, Claudio, additional
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- 2023
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9. Diffusion Weighted Imaging in Neuro-Oncology: Diagnosis, Post-Treatment Changes, and Advanced Sequences—An Updated Review
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Romano, Andrea, primary, Palizzi, Serena, additional, Romano, Allegra, additional, Moltoni, Giulia, additional, Di Napoli, Alberto, additional, Maccioni, Francesca, additional, and Bozzao, Alessandro, additional
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- 2023
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10. Cardiotoxicity, Cardioprotection, and Prognosis in Survivors of Anticancer Treatment Undergoing Cardiac Surgery: Unmet Needs
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Vittorio Palmieri, Maria Teresa Vietri, Andrea Montalto, Andrea Montisci, Francesco Donatelli, Enrico Coscioni, Claudio Napoli, Palmieri, V., Vietri, M. T., Montalto, A., Montisci, A., Donatelli, F., Coscioni, E., and Napoli, C.
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Cancer Research ,Oncology ,Anticancer Treatment ,Settore MED/05 - Patologia Clinica ,cancer ,Settore MED/11 - Malattie dell'Apparato Cardiovascolare ,Settore MED/23 - Chirurgia Cardiaca ,Cardiotoxicity ,Cardioprotection ,Cardiac Surgery ,prognosis ,cardiac surgery - Abstract
Background: Anticancer treatments are improving the prognosis of patients fighting cancer. However, anticancer treatments may also increase the cardiovascular (CV) risk by increasing metabolic disorders. Atherosclerosis and atherothrombosis related to anticancer treatments may lead to ischemic heart disease (IHD), while direct cardiac toxicity may induce non-ischemic heart disease. Moreover, valvular heart disease (VHD), aortic syndromes (AoS), and advanced heart failure (HF) associated with CV risk factors and preclinical CV disease as well as with chronic inflammation and endothelial dysfunction may also occur in survivors of anti-carcer treatments. Methods: Public electronic libraries have been searched systematically looking at cardiotoxicity, cardioprotection, CV risk and disease, and prognosis after cardiac surgery in survivors of anticancer treatments. Results: CV risk factors and disease may not be infrequent among survivors of anticancer treatments. As cardiotoxicity of established anticancer treatments has been investigated and is frequently irreversible, cardiotoxicity associated with novel treatments appears to be more frequently reversible, but also potentially synergic. Small reports suggest that drugs preventing HF in the general population may be effective also among survivors of anticancer treatments, so that CV risk factors and disease, and chronic inflammation, may lead to indication to cardiac surgery in survivors of anticancer treatments. There is a lack of substantial data on whether current risk scores are efficient to predict prognosis after cardiac surgery in survivors of anticancer treatments, and to guide tailored decision-making. IHD is the most common condition requiring cardiac surgery among survivors of anticancer treatments. Primary VHD is mostly related to a history of radiation therapy. No specific reports exist on AoS in survivors of anticancer treatments. Conclusions: It is unclear whether interventions to dominate cancer- and anticancer treatment-related metabolic syndromes, chronic inflammation, and endothelial dysfunction, leading to IHD, nonIHD, VHD, HF, and AoS, are as effective in survivors of anticancer treatments as in the general population. When CV diseases require cardiac surgery, survivors of anticancer treatments may be a population at specifically elevated risk, rather than affected by a specific risk factor.
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- 2023
11. Adequacy of Pain Treatment in Radiotherapy Departments: Results of a Multicenter Study on 2104 Patients (Arise)
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Donati, Costanza M., primary, Nardi, Elena, additional, Zamagni, Alice, additional, Siepe, Giambattista, additional, Mammini, Filippo, additional, Cellini, Francesco, additional, Di Rito, Alessia, additional, Portaluri, Maurizio, additional, De Tommaso, Cristina, additional, Santacaterina, Anna, additional, Tamburella, Consuelo, additional, Di Franco, Rossella, additional, Parisi, Salvatore, additional, Cossa, Sabrina, additional, Fusco, Vincenzo, additional, Bianculli, Antonella, additional, Ziccarelli, Pierpaolo, additional, Ziccarelli, Luigi, additional, Genovesi, Domenico, additional, Caravatta, Luciana, additional, Deodato, Francesco, additional, Macchia, Gabriella, additional, Fiorica, Francesco, additional, Napoli, Giuseppe, additional, Buwenge, Milly, additional, Rossi, Romina, additional, Maltoni, Marco, additional, and Morganti, Alessio G., additional
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- 2022
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12. Safety of Inhomogeneous Dose Distribution IMRT for High-Grade Glioma Reirradiation: A Prospective Phase I/II Trial (GLIORAD TRIAL)
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Ciammella, Patrizia, primary, Cozzi, Salvatore, additional, Botti, Andrea, additional, Giaccherini, Lucia, additional, Sghedoni, Roberto, additional, Orlandi, Matteo, additional, Napoli, Manuela, additional, Pascarella, Rosario, additional, Pisanello, Anna, additional, Russo, Marco, additional, Cavallieri, Francesco, additional, Ruggieri, Maria Paola, additional, Cavuto, Silvio, additional, Savoldi, Luisa, additional, Iotti, Cinzia, additional, and Iori, Mauro, additional
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- 2022
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13. Cardiac Toxicity Associated with Cancer Immunotherapy and Biological Drugs
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Montisci A., Vietri M. T., Palmieri V., Sala S., Donatelli F., Napoli C., Montisci, A., Vietri, M. T., Palmieri, V., Sala, S., Donatelli, F., and Napoli, C.
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immune checkpoint inhibitors ,trastuzumab ,chimeric antigen receptor-modified T (CAR-T) ,Myocarditi ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,cancer ,Immune checkpoint inhibitor ,Review ,immunotherapy ,myocarditis ,RC254-282 - Abstract
Simple Summary Immunotherapy is increasingly being used to treat solid tumors and lymphoproliferative diseases. The main classes of drugs are: HER-2-targeted therapies, CTLA-blockers, PD/PDL-1 inhibitors, CAR-T therapy. All these drugs are associated with meaningful cardiac toxicity, ranging from a transient decline of left ventricular function with complete reversibility to myocarditis with a high fatality rate. Abstract Cancer immunotherapy significantly contributed to an improvement in the prognosis of cancer patients. Immunotherapy, including human epidermal growth factor receptor 2 (HER2)-targeted therapies, immune checkpoint inhibitors (ICI), and chimeric antigen receptor-modified T (CAR-T), share the characteristic to exploit the capabilities of the immune system to kill cancerous cells. Trastuzumab is a monoclonal antibody against HER2 that prevents HER2-mediated signaling; it is administered mainly in HER2-positive cancers, such as breast, colorectal, biliary tract, and non-small-cell lung cancers. Immune checkpoint inhibitors (ICI) inhibit the binding of CTLA-4 or PD-1 to PDL-1, allowing T cells to kill cancerous cells. ICI can be used in melanomas, non-small-cell lung cancer, urothelial, and head and neck cancer. There are two main types of T-cell transfer therapy: tumor-infiltrating lymphocytes (or TIL) therapy and chimeric antigen receptor-modified T (CAR-T) cell therapy, mainly applied for B-cell lymphoma and leukemia and mantle-cell lymphoma. HER2-targeted therapies, mainly trastuzumab, are associated with left ventricular dysfunction, usually reversible and rarely life-threatening. PD/PDL-1 inhibitors can cause myocarditis, rare but potentially fulminant and associated with a high fatality rate. CAR-T therapy is associated with several cardiac toxic effects, mainly in the context of a systemic adverse effect, the cytokines release syndrome.
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- 2021
14. Adequacy of Pain Treatment in Radiotherapy Departments: Results of a Multicenter Study on 2104 Patients (Arise)
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Costanza M. Donati, Elena Nardi, Alice Zamagni, Giambattista Siepe, Filippo Mammini, Francesco Cellini, Alessia Di Rito, Maurizio Portaluri, Cristina De Tommaso, Anna Santacaterina, Consuelo Tamburella, Rossella Di Franco, Salvatore Parisi, Sabrina Cossa, Vincenzo Fusco, Antonella Bianculli, Pierpaolo Ziccarelli, Luigi Ziccarelli, Domenico Genovesi, Luciana Caravatta, Francesco Deodato, Gabriella Macchia, Francesco Fiorica, Giuseppe Napoli, Milly Buwenge, Romina Rossi, Marco Maltoni, Alessio G. Morganti, Donati, Costanza M, Nardi, Elena, Zamagni, Alice, Siepe, Giambattista, Mammini, Filippo, Cellini, Francesco, Di Rito, Alessia, Portaluri, Maurizio, De Tommaso, Cristina, Santacaterina, Anna, Tamburella, Consuelo, Di Franco, Rossella, Parisi, Salvatore, Cossa, Sabrina, Fusco, Vincenzo, Bianculli, Antonella, Ziccarelli, Pierpaolo, Ziccarelli, Luigi, Genovesi, Domenico, Caravatta, Luciana, Deodato, Francesco, Macchia, Gabriella, Fiorica, Francesco, Napoli, Giuseppe, Buwenge, Milly, Rossi, Romina, Maltoni, Marco, and Morganti, Alessio G
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Cancer Research ,pain management index ,Oncology ,observational study ,pain ,multicenter ,radiotherapy - Abstract
Simple Summary Cancer pain is often inadequately treated, as shown by several clinical studies. This problem has been confirmed in different clinical settings but the reasons for this phenomenon are unclear. Furthermore, little evidence is available on the adequacy of pharmacological pain management in patients undergoing radiotherapy. Moreover, studies investigating possible predictors of inadequate pain management reported contradictory results. Therefore, in this analysis, we evaluated a large population of cancer patients undergoing radiotherapy. We recorded, similarly to previous studies, a 45% rate of patients with inadequate analgesic therapy. Furthermore, evaluating the characteristics of patients with inadequate analgesic treatment, we noted that the subjects with better general conditions or better prognostic factors are those most frequently receiving inadequate drug therapy. Aim: The frequent inadequacy of pain management in cancer patients is well known. Moreover, the quality of analgesic treatment in patients treated with radiotherapy (RT) has only been rarely assessed. In order to study the latter topic, we conducted a multicenter, observational and prospective study based on the Pain Management Index (PMI) in RT Italian departments. Methods: We collected data on age, gender, tumor site and stage, performance status, treatment aim, and pain (type: CP-cancer pain, NCP-non-cancer pain, MP-mixed pain; intensity: NRS: Numeric Rating Scale). Furthermore, we analyzed the impact on PMI on these parameters, and we defined a pain score with values from 0 (NRS: 0, no pain) to 3 (NRS: 7-10: intense pain) and an analgesic score from 0 (pain medication not taken) to 3 (strong opioids). By subtracting the pain score from the analgesic score, we obtained the PMI value, considering cases with values < 0 as inadequate analgesic prescriptions. The Ethics Committees of the participating centers approved the study (ARISE-1 study). Results: Two thousand one hundred four non-selected outpatients with cancer and aged 18 years or older were enrolled in 13 RT departments. RT had curative and palliative intent in 62.4% and 37.6% patients, respectively. Tumor stage was non-metastatic in 57.3% and metastatic in 42.7% of subjects, respectively. Pain affected 1417 patients (CP: 49.5%, NCP: 32.0%; MP: 18.5%). PMI was < 0 in 45.0% of patients with pain. At multivariable analysis, inadequate pain management was significantly correlated with curative RT aim, ECOG performance status = 1 (versus both ECOG-PS3 and ECOG- PS4), breast cancer, non-cancer pain, and Central and South Italy RT Departments (versus Northern Italy).Conclusions: Pain management was less adequate in patients with more favorable clinical condition and stage. Educational and organizational strategies are needed in RT departments to reduce the non-negligible percentage of patients with inadequate analgesic therapy.
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- 2022
15. Enhancer RNAs (eRNAs) in Cancer: The Jacks of All Trades
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Sara Napoli, Nicolas Munz, Francesca Guidetti, and Francesco Bertoni
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Cancer Research ,Oncology - Abstract
Enhancer RNAs (eRNAs) are non-coding RNAs (ncRNAs) transcribed in enhancer regions. They play an important role in transcriptional regulation, mainly during cellular differentiation. eRNAs are tightly tissue- and cell-type specific and are induced by specific stimuli, activating promoters of target genes in turn. eRNAs usually have a very short half-life but in some cases, once activated, they can be stably expressed and acquire additional functions. Due to their critical role, eRNAs are often dysregulated in cancer and growing number of interactions with chromatin modifiers, transcription factors, and splicing machinery have been described. Enhancer activation and eRNA transcription have particular relevance also in inflammatory response, placing the eRNAs at the interplay between cancer and immune cells. Here, we summarize all the possible molecular mechanisms recently reported in association with eRNAs activity.
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- 2022
16. Enhancer RNAs (eRNAs) in Cancer: The Jacks of All Trades
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Napoli, Sara, primary, Munz, Nicolas, additional, Guidetti, Francesca, additional, and Bertoni, Francesco, additional
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- 2022
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17. Prostate Cancer and Sleep Disorders: A Systematic Review
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Sparasci, Davide, primary, Napoli, Ilenia, additional, Rossi, Lorenzo, additional, Pereira-Mestre, Ricardo, additional, Manconi, Mauro, additional, Treglia, Giorgio, additional, Marandino, Laura, additional, Ottaviano, Margaret, additional, Turco, Fabio, additional, Mangan, Dylan, additional, Gillessen, Silke, additional, and Vogl, Ursula Maria, additional
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- 2022
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18. Diffusion Weighted Imaging in Neuro-Oncology: Diagnosis, Post-Treatment Changes, and Advanced Sequences—An Updated Review
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Andrea Romano, Serena Palizzi, Allegra Romano, Giulia Moltoni, Alberto Di Napoli, Francesca Maccioni, and Alessandro Bozzao
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tumors ,diffusion-weighted imaging ,magnetic resonance imaging ,Cancer Research ,Oncology - Abstract
DWI is an imaging technique commonly used for the assessment of acute ischemia, inflammatory disorders, and CNS neoplasia. It has several benefits since it is a quick, easily replicable sequence that is widely used on many standard scanners. In addition to its normal clinical purpose, DWI offers crucial functional and physiological information regarding brain neoplasia and the surrounding milieu. A narrative review of the literature was conducted based on the PubMed database with the purpose of investigating the potential role of DWI in the neuro-oncology field. A total of 179 articles were included in the study.
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- 2023
19. Targeting KRAS in NSCLC: Old Failures and New Options for “Non-G12c” Patients
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Jacobs, Francesca, primary, Cani, Massimiliano, additional, Malapelle, Umberto, additional, Novello, Silvia, additional, Napoli, Valerio Maria, additional, and Bironzo, Paolo, additional
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- 2021
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20. RNA Sequencing of Primary Cutaneous and Breast-Implant Associated Anaplastic Large Cell Lymphomas Reveals Infrequent Fusion Transcripts and Upregulation of PI3K/AKT Signaling via Neurotrophin Pathway Genes
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Di Napoli, Arianna, primary, Vacca, Davide, additional, Bertolazzi, Giorgio, additional, Lopez, Gianluca, additional, Piane, Maria, additional, Germani, Aldo, additional, Rogges, Evelina, additional, Pepe, Giuseppina, additional, Santanelli Di Pompeo, Fabio, additional, Salgarello, Marzia, additional, Jobanputra, Vaidehi, additional, Hsiao, Susan, additional, Wrzeszczynski, Kazimierz O., additional, Berti, Emilio, additional, and Bhagat, Govind, additional
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- 2021
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21. Beyond Abscopal Effect: A Meta-Analysis of Immune Checkpoint Inhibitors and Radiotherapy in Advanced Non-Small Cell Lung Cancer
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Paolo Pinton, Andrea Bonetti, Massimiliano Berretta, Jacopo Giuliani, Mariasole Perrone, Andrea Remo, Nicoletta Luca, Milena Gabbani, Umberto Tebano, Francesco Fiorica, Carlotta Giorgi, Sonia Missiroli, Giuseppe Napoli, Eva Pigozzi, Daniela Grigolato, and Andrea Tontini
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Immune checkpoint inhibitors ,Population ,MEDLINE ,Article ,NO ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Combination of immune checkpoint inhibitors and radiotherapy ,Immunotherapy ,Radiation oncology ,Radiation oncology and immunity ,education ,Lung cancer ,RC254-282 ,education.field_of_study ,radiation oncology and immunity ,business.industry ,Abscopal effect ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,radiation oncology ,Combination of immune checkpoint inhibitors and radiotherapy, Immunotherapy, Radiation oncology, Radiation oncology and immunity ,medicine.disease ,Radiation therapy ,030104 developmental biology ,030220 oncology & carcinogenesis ,Meta-analysis ,combination of immune checkpoint inhibitors and radiotherapy ,immunotherapy ,business - Abstract
Background: Immune checkpoint inhibitors (ICI) plus radiotherapy (RT) have been suggested as an emerging combination in non-small cell lung cancer (NSCLC) patients. However, little is known about the magnitude of its benefits and potential clinical predictors. Objective: To assess the effects of this combination on the increase in overall and progression-free survival. Data sources: The MEDLINE and CANCERLIT (1970–2020) electronic databases were searched, and the reference lists of included studies were manually searched. Study selection: Studies were included if they were comparative studies between combination ICI-RT and ICI or RT alone in advanced or metastatic NSCLC patients. Overall survival (OS) was analyzed according to the treatment strategy. Data extraction: Data on population, intervention, and outcomes were extracted from each study, in accordance with the intention-to-treat method, by two independent observers and combined using the DerSimonian method and Laird method. Results: Compared to ICI or RT alone, ICI-RT significantly increased the 1-year and 3-year OS RR by 0.75 (95% CI 0.64–0.88, p = 0.0003) and 0.85 (95% CI 0.78–0.93, p = 0.0006), respectively. Furthermore, there was a statistically significant benefit on 1- and 3-year progression-free survival (RR 0.73 (95% CI, 0.61–0.87, p = 0.0005) and RR 0.82 (95% CI 0.67–0.99, p = 0.04), respectively). Conclusions: In patients with advanced or metastatic NSCLC, combination ICI-RT increases 1- and 3-year OS and progression-free survival compared to ICI or RT alone.
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- 2021
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22. Evaluation of the Preclinical Efficacy of Lurbinectedin in Malignant Pleural Mesothelioma
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Riccardo Taulli, Marcello Francesco Lingua, Federica Di Nicolantonio, Alessandra Pittaro, Giorgio V. Scagliotti, Deborah Morena, Chiara Riganti, Roberta Libener, Federico Bussolino, Francesco Leo, Alberto Sandri, Mauro Papotti, Luisella Righi, Paolo Bironzo, Chiara Gigliotti, Valentina Comunanza, Silvia Novello, Francesco Guerrera, Francesca Napoli, Francesca Picca, Pablo M. Aviles, and Dario Pasquale Anobile
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Cancer Research ,BAP1 ,Tumor microenvironment ,Chemotherapy ,Cell cycle checkpoint ,business.industry ,DNA damage ,medicine.medical_treatment ,MPM ,lurbinectedin ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Cell cycle ,DNA damage response ,Article ,Oncology ,Cancer research ,Lurbinectedin ,Medicine ,DNA fragmentation ,Viability assay ,business ,RC254-282 - Abstract
Simple Summary The marine drug lurbinectedin revealed an unprecedented efficacy against patient-derived malignant pleural mesothelioma cells, regardless of the histological type and the BAP1 mutation status. By inducing strong DNA damages, it dramatically arrested cell cycle progression and induced apoptosis. These results may be translated into the use of lurbinectedin as an effective agent for malignant pleural mesothelioma patients. Abstract Background: Malignant pleural mesothelioma (MPM) is a highly aggressive cancer generally diagnosed at an advanced stage and characterized by a poor prognosis. The absence of alterations in druggable kinases, together with an immune-suppressive tumor microenvironment, limits the use of molecular targeted therapies, making the treatment of MPM particularly challenging. Here we investigated the in vitro susceptibility of MPM to lurbinectedin (PM01183), a marine-derived drug that recently received accelerated approval by the FDA for the treatment of patients with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy. Methods: A panel of primary MPM cultures, resembling the three major MPM histological subtypes (epithelioid, sarcomatoid, and biphasic), was characterized in terms of BAP1 status and histological markers. Subsequently, we explored the effects of lurbinectedin at nanomolar concentration on cell cycle, cell viability, DNA damage, genotoxic stress response, and proliferation. Results: Stabilized MPM cultures exhibited high sensitivity to lurbinectedin independently from the BAP1 mutational status and histological classification. Specifically, we observed that lurbinectedin rapidly promoted a cell cycle arrest in the S-phase and the activation of the DNA damage response, two conditions that invariably resulted in an irreversible DNA fragmentation, together with strong apoptotic cell death. Moreover, the analysis of long-term treatment indicated that lurbinectedin severely impacts MPM transforming abilities in vitro. Conclusion: Overall, our data provide evidence that lurbinectedin exerts a potent antitumoral activity on primary MPM cells, independently from both the histological subtype and BAP1 alteration, suggesting its potential activity in the treatment of MPM patients.
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- 2021
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23. Pathological Characterization of Tumor Immune Microenvironment (TIME) in Malignant Pleural Mesothelioma
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Napoli, Francesca, primary, Listì, Angela, additional, Zambelli, Vanessa, additional, Witel, Gianluca, additional, Bironzo, Paolo, additional, Papotti, Mauro, additional, Volante, Marco, additional, Scagliotti, Giorgio, additional, and Righi, Luisella, additional
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- 2021
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24. Beyond Abscopal Effect: A Meta-Analysis of Immune Checkpoint Inhibitors and Radiotherapy in Advanced Non-Small Cell Lung Cancer
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Fiorica, Francesco, primary, Tebano, Umberto, additional, Gabbani, Milena, additional, Perrone, Mariasole, additional, Missiroli, Sonia, additional, Berretta, Massimiliano, additional, Giuliani, Jacopo, additional, Bonetti, Andrea, additional, Remo, Andrea, additional, Pigozzi, Eva, additional, Tontini, Andrea, additional, Napoli, Giuseppe, additional, Luca, Nicoletta, additional, Grigolato, Daniela, additional, Pinton, Paolo, additional, and Giorgi, Carlotta, additional
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- 2021
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25. Evaluation of the Preclinical Efficacy of Lurbinectedin in Malignant Pleural Mesothelioma
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Anobile, Dario P., primary, Bironzo, Paolo, additional, Picca, Francesca, additional, Lingua, Marcello F., additional, Morena, Deborah, additional, Righi, Luisella, additional, Napoli, Francesca, additional, Papotti, Mauro G., additional, Pittaro, Alessandra, additional, Di Nicolantonio, Federica, additional, Gigliotti, Chiara, additional, Bussolino, Federico, additional, Comunanza, Valentina, additional, Guerrera, Francesco, additional, Sandri, Alberto, additional, Leo, Francesco, additional, Libener, Roberta, additional, Aviles, Pablo, additional, Novello, Silvia, additional, Taulli, Riccardo, additional, Scagliotti, Giorgio V., additional, and Riganti, Chiara, additional
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- 2021
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26. Hybrid 18F-FDG-PET/MRI Measurement of Standardized Uptake Value Coupled with Yin Yang 1 Signature in Metastatic Breast Cancer. A Preliminary Study
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Schiano Concetta, Franzese Monica, Pane Katia, Garbino Nunzia, Soricelli Andrea, Salvatore Marco, de Nigris Filomena, Napoli Claudio, SCHIANO, Concetta, Schiano, Concetta, Franzese, Monica, Pane, Katia, Garbino, Nunzia, Soricelli, Andrea, Salvatore, Marco, de NIGRIS, Filomena, and Napoli, Claudio
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Estrogen receptor ,Standardized uptake value ,lcsh:RC254-282 ,Peripheral blood mononuclear cell ,Article ,Metastasis ,Imaging ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Internal medicine ,medicine ,Standardized Uptake Value Maximum ,Breast ,Yin Yang 1 ,Stage (cooking) ,Radiomics ,business.industry ,Marker ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Metastatic breast cancer ,030104 developmental biology ,030220 oncology & carcinogenesis ,Radiomic ,business - Abstract
Purpose: Detection of breast cancer (BC) metastasis at the early stage is important for the assessment of BC progression status. Image analysis represents a valuable tool for the management of oncological patients. Our preliminary study combined imaging parameters from hybrid 18F-FDG-PET/MRI and the expression level of the transcriptional factor Yin Yang 1 (YY1) for the detection of early metastases. Methods: The study enrolled suspected n = 217 BC patients that underwent 18F-FDG-PET/MRI scans. The analysis retrospectively included n = 55 subjects. n = 40 were BC patients and n = 15 imaging-negative female individuals were healthy subjects (HS). Standard radiomics parameters were extracted from PET/MRI image. RNA was obtained from peripheral blood mononuclear cells and YY1 expression level was evaluated by real time reverse transcription polymerase chain reactions (qRT-PCR). An enzyme-linked immuosorbent assay (ELISA) was used to determine the amount of YY1 serum protein. Statistical comparison between subgroups was evaluated by Mann-Whitney U and Spearman&rsquo, s tests. Results: Radiomics showed a significant positive correlation between Greg-level co-occurrence matrix (GLCM) and standardized uptake value maximum (SUVmax) (r = 0.8 and r = 0.8 respectively) in BC patients. YY1 level was significant overexpressed in estrogen receptor (ER)-positive/progesteron receptor-positive/human epidermal growth factor receptor2-negative (ER+/PR+/HER2-) subtype of BC patients with synchronous metastasis (SM) at primary diagnosis compared to metachronous metastasis (MM) and HS (p <, 0.001) and correlating significantly with 18F-FDG-uptake parameter (SUVmax) (r = 0.48). Conclusions: The combination of functional 18F-FDG-PET/MRI parameters and molecular determination of YY1 could represent a novel integrated approach to predict synchronous metastatic disease with more accuracy than 18F-FDG-PET/MRI alone.
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- 2019
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27. Bortezomib-Loaded Mesoporous Silica Nanoparticles Selectively Alter Metabolism and Induce Death in Multiple Myeloma Cells
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Ida Perrotta, Michele Pellegrino, Mariarosa Fava, Luca Frattaruolo, Elena Claire Ricci, Diego Sisci, Marianna Greco, Francesca Giordano, Antonella Leggio, Anna Rita Cappello, Alessandra Comandè, Alessandra Nigro, Catia Morelli, Marzia De Santo, Luigi Pasqua, and Ilaria Ester De Napoli
- Subjects
0301 basic medicine ,Cancer Research ,animal structures ,Cell ,medicine.disease_cause ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,0302 clinical medicine ,mitochondrial dysfunction ,energy metabolism ,medicine ,oxidative stress ,mesoporous silica nanoparticles ,Multiple myeloma ,TUNEL assay ,Bortezomib ,Chemistry ,target therapy ,bortezomib ,apoptosis ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Blot ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Apoptosis ,Folate receptor ,030220 oncology & carcinogenesis ,Cancer research ,sense organs ,Multiple Myeloma ,Oxidative stress ,medicine.drug - Abstract
A mesoporous silica-based nanodevice bearing the antineoplastic drug bortezomib (BTZ), whose release is triggered in acidic environment and grafted with folic acid (FOL) as a targeting function (FOL-MSN-BTZ) was tested on folate receptor overexpressing (FR+) multiple myeloma (MM) cells and on FR negative (FR&minus, ) normal cells. FOL-MSN-BTZ efficacy studies were conducted by means of growth experiments, TEM, TUNEL assay and Western Blotting analysis (WB). Metabolic investigations were performed to assess cells metabolic response to MSNs treatments. FOL-MSN-BTZ exclusively killed FR+ MM cells, leading to an apoptotic rate that was comparable to that induced by free BTZ, and the effect was accompanied by metabolic dysfunction and oxidative stress. Importantly, FOL-MSN-BTZ treated FR&minus, normal cells did not show any significant sign of injury or metabolic perturbation, while free BTZ was still highly toxic. Notably, the vehicle alone (MSN-FOL) did not affect any biological process in both tested cell models. These data show the striking specificity of FOL-MSN-BTZ toward FR+ tumor cells and the outstanding safety of the MSN-FOL vehicle, paving the way for a future exploitation of FOL-MSN-BTZ in MM target therapy.
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- 2020
28. Role of ETS1 in the Transcriptional Network of Diffuse Large B Cell Lymphoma of the Activated B Cell-Like Type
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Priebe, Valdemar, Sartori, Giulio, Napoli, Sara, Chung, Elaine Yee Lin, Cascione, Luciano, Kwee, Ivo, Arribas, Alberto Jesus, Mensah, Afua Adjeiwaa, Rinaldi, Andrea, Ponzoni, Maurilio, Zucca, Emanuele, Rossi, Davide, Efremov, Dimitar, Lenz, Georg, Thome, Margot, and Bertoni, Francesco
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immune system diseases ,ETS1 ,hemic and lymphatic diseases ,BCL6 ,PRDM1 ,diffuse large B cell lymphoma ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,lcsh:RC254-282 ,Article - Abstract
Diffuse large B cell lymphoma (DLBCL) is a heterogenous disease that has been distinguished into at least two major molecular entities, the germinal center-like B cell (GCB) DLBCL and activated-like B cell (ABC) DLBCL, based on transcriptome expression profiling. A recurrent ch11q24.3 gain is observed in roughly a fourth of DLBCL cases resulting in the overexpression of two ETS transcription factor family members, ETS1 and FLI1. Here, we knocked down ETS1 expression by siRNA and analyzed expression changes integrating them with ChIP-seq data to identify genes directly regulated by ETS1. ETS1 silencing affected expression of genes involved in B cell signaling activation, B cell differentiation, cell cycle, and immune processes. Integration of RNA-Seq (RNA sequencing) data and ChIP-Seq (chromatin immunoprecipitation sequencing) identified 97 genes as bona fide, positively regulated direct targets of ETS1 in ABC-DLBCL. Among these was the Fc receptor for IgM, FCMR (also known as FAIM3 or Toso), which showed higher expression in ABC- than GCB-DLBCL clinical specimens. These findings show that ETS1 is contributing to the lymphomagenesis in a subset of DLBCL and identifies FCMR as a novel target of ETS1, predominantly expressed in ABC-DLBCL.
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- 2020
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29. Cytoreductive Surgery for Heavily Pre-Treated, Platinum-Resistant Epithelial Ovarian Carcinoma: A Two-Center Retrospective Experience
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M. Robella, Giorgio Valabrega, Eleonora Ghisoni, Riccardo Ponzone, Cono Scaffa, Giulia Scotto, Margherita Turinetto, Massimo Di Maio, Dimitris Siatis, Marco Vaira, Stefano Greggi, Gaia Giannone, Sandro Pignata, Valentina Tuninetti, Marilena Di Napoli, Michele De Simone, and Furio Maggiorotto
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Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,0302 clinical medicine ,medicine ,cytoreductive surgery ,030212 general & internal medicine ,Prospective cohort study ,Platinum resistant ,Chemotherapy ,epithelial ovarian carcinoma ,business.industry ,Hazard ratio ,Retrospective cohort study ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,platinum resistance ,Surgery ,Oncology ,Epithelial ovarian carcinoma ,030220 oncology & carcinogenesis ,Ovarian carcinomas ,business ,Cytoreductive surgery - Abstract
Few retrospective studies have shown a benefit in selected patients affected by heavily pre-treated, platinum-resistant ovarian carcinomas (PROCs) who have undergone cytoreduction at relapse. However, the role of tertiary and quaternary cytoreductive surgery is not fully defined. Our aim was to evaluate survival and surgical morbidity and mortality after maximal cytoreduction in this setting. We evaluated all consecutive patients undergoing cytoreduction for platinum-resistance over an 8-year period (2010&ndash, 2018) in two different centers. Fifty patients (median age 52.5 years, range 34&ndash, 75) were included, the median number of previous chemotherapy lines was three (range 1&ndash, 7) and the median number of previous surgeries was one (range 1&ndash, 4). Completeness of cytoreduction (CC = 0) was achieved in 22 patients (44%). Rates of major operative morbidity and 30-day mortality were 38% and 8%, respectively. Median follow-up was 35 months. The absence of tumor residual (CC = 0) was associated with a significantly better overall survival (OS) compared to the CC >, 0 subgroup (median OS 32.9 months (95%CI 21.6&ndash, 44.2) vs. 4.8 months (95% CI n.a.&ndash, 9.8), hazard ratio (HR) 4.21 (95%CI 2.07&ndash, 8.60), p <, 0.001). Optimal cytoreduction is feasible and associated with promising OS in selected, heavily pre-treated PROCs. Further prospective studies are required to better define the role of surgery in platinum-resistant disease.
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- 2020
30. Impact of Advanced Age on the Clinical Presentation and Outcome of Sporadic Medullary Thyroid Carcinoma
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Matrone, Antonio, primary, Gambale, Carla, additional, Prete, Alessandro, additional, Piaggi, Paolo, additional, Cappagli, Virginia, additional, Bottici, Valeria, additional, Romei, Cristina, additional, Ciampi, Raffaele, additional, Torregrossa, Liborio, additional, De Napoli, Luigi, additional, Molinaro, Eleonora, additional, Materazzi, Gabriele, additional, Basolo, Fulvio, additional, and Elisei, Rossella, additional
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- 2020
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31. Bortezomib-Loaded Mesoporous Silica Nanoparticles Selectively Alter Metabolism and Induce Death in Multiple Myeloma Cells
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Nigro, Alessandra, primary, Frattaruolo, Luca, additional, Fava, Mariarosa, additional, De Napoli, Ilaria, additional, Greco, Marianna, additional, Comandè, Alessandra, additional, De Santo, Marzia, additional, Pellegrino, Michele, additional, Ricci, Elena, additional, Giordano, Francesca, additional, Perrotta, Ida, additional, Leggio, Antonella, additional, Pasqua, Luigi, additional, Sisci, Diego, additional, Cappello, Anna Rita, additional, and Morelli, Catia, additional
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- 2020
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32. Cytoreductive Surgery for Heavily Pre-Treated, Platinum-Resistant Epithelial Ovarian Carcinoma: A Two-Center Retrospective Experience
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Tuninetti, Valentina, primary, Di Napoli, Marilena, additional, Ghisoni, Eleonora, additional, Maggiorotto, Furio, additional, Robella, Manuela, additional, Scotto, Giulia, additional, Giannone, Gaia, additional, Turinetto, Margherita, additional, Siatis, Dimitris, additional, Ponzone, Riccardo, additional, Vaira, Marco, additional, De Simone, Michele, additional, Scaffa, Cono, additional, Pignata, Sandro, additional, Greggi, Stefano, additional, Di Maio, Massimo, additional, and Valabrega, Giorgio, additional
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- 2020
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33. Early Tumor Shrinkage and Depth of Response Evaluation in Metastatic Pancreatic Cancer Treated with First Line Chemotherapy: An Observational Retrospective Cohort Study
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Vivaldi, Caterina, primary, Fornaro, Lorenzo, additional, Cappelli, Carla, additional, Pecora, Irene, additional, Catanese, Silvia, additional, Salani, Francesca, additional, Cacciato Insilla, Andrea, additional, Kauffmann, Emanuele, additional, Donati, Francescamaria, additional, Pasquini, Giulia, additional, Massa, Valentina, additional, Napoli, Niccolò, additional, Lencioni, Monica, additional, Boraschi, Piero, additional, Campani, Daniela, additional, Boggi, Ugo, additional, Caramella, Davide, additional, Falcone, Alfredo, additional, and Vasile, Enrico, additional
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- 2019
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34. Early Tumor Shrinkage and Depth of Response Evaluation in Metastatic Pancreatic Cancer Treated with First Line Chemotherapy: An Observational Retrospective Cohort Study
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Caterina Vivaldi, Valentina Massa, Piero Boraschi, Davide Caramella, Enrico Vasile, Emanuele Federico Kauffmann, Carla Cappelli, Irene Pecora, Daniela Campani, Ugo Boggi, Lorenzo Fornaro, Giulia Pasquini, Andrea Cacciato Insilla, Monica Lencioni, Francesca Salani, Francescamaria Donati, Alfredo Falcone, Silvia Catanese, and Niccolò Napoli
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Multivariate analysis ,Colorectal cancer ,pancreatic cancer ,Population ,lcsh:RC254-282 ,Article ,depth of response ,03 medical and health sciences ,0302 clinical medicine ,gemcitabine plus nab-paclitaxel ,Pancreatic cancer ,Internal medicine ,Medicine ,education ,FOLFOXIRI ,education.field_of_study ,business.industry ,Combination chemotherapy ,Retrospective cohort study ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Gemcitabine ,030104 developmental biology ,early tumor shrinkage ,030220 oncology & carcinogenesis ,business ,medicine.drug - Abstract
Early tumor shrinkage (ETS) and depth of response (DoR) predict favorable outcomes in metastatic colorectal cancer. We aim to evaluate their prognostic role in metastatic pancreatic cancer (PC) patients treated with first-line modified-FOLFIRINOX (FOLFOXIRI) or Gemcitabine + Nab-paclitaxel (GemNab). Hence, 138 patients were tested for ETS, defined as a &ge, 20% reduction in the sum of target lesions&rsquo, longest diameters (SLD) after 6&ndash, 8 weeks from baseline, and DoR, i.e., the maximum percentage shrinkage in the SLD from baseline. Association of ETS and DoR with progression-free survival (PFS) and overall survival (OS) was assessed. ETS was reached in 49 patients (39.5% in the FOLFOXIRI, 29.8% in the GemNab group, p = 0.280). In the overall population, ETS was significantly associated with better PFS (8.0 vs. 4.8 months, p <, 0.001) and OS (13.2 vs. 9.7 months, p = 0.001). Median DoR was &minus, 27.5% (&minus, 29.4% with FOLFOXIRI and &minus, 21.4% with GemNab, p = 0.016): DoR was significantly associated with better PFS (9.0 vs. 6.7 months, p <, 0.001) and OS (14.3 vs. 11.1 months, p = 0.031). Multivariate analysis confirmed both ETS and DoR are independently associated with PFS and OS. In conclusion, our study added evidence on the role of ETS and DoR in the prediction of outcome of PC patients treated with first-line combination chemotherapy.
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- 2019
35. Impact of Advanced Age on the Clinical Presentation and Outcome of Sporadic Medullary Thyroid Carcinoma.
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Matrone, Antonio, Gambale, Carla, Prete, Alessandro, Piaggi, Paolo, Cappagli, Virginia, Bottici, Valeria, Romei, Cristina, Ciampi, Raffaele, Torregrossa, Liborio, De Napoli, Luigi, Molinaro, Eleonora, Materazzi, Gabriele, Basolo, Fulvio, and Elisei, Rossella
- Subjects
CANCER cells ,THYROID gland tumors ,AGE distribution ,METASTASIS ,KAPLAN-Meier estimator ,SURVIVAL analysis (Biometry) ,DESCRIPTIVE statistics ,LONGITUDINAL method ,SYMPTOMS - Abstract
Simple Summary: The clinical behavior of medullary thyroid carcinoma is heterogeneous and can be influenced by several clinical, biochemical and molecular factors. The role of age as a prognostic factor remains controversial. In our cohort of 432 sporadic medullary thyroid carcinoma, no differences in histologic features at diagnosis and in number and type of therapies performed during the follow-up were detected when dividing the patients according to age (< and ≥ 65 years). Younger patients had a longer follow-up and survival time, compared to the older patients. However, in dead patients, no differences in the aggressiveness of the disease at presentation and treatments performed during the follow-up were found between the two age groups. Sporadic medullary thyroid carcinoma (MTC) is a rare malignancy with a heterogeneous clinical course. Several potential prognostic factors have been investigated, but the impact of some of these is controversial, such as age at diagnosis. We evaluated the data of 432 sporadic MTC patients followed-up for a median of 7.4 years. Patients were divided and compared according to their age at diagnosis in group A (<65 years—n = 338, 78.2%) and group B (≥65 years—n = 94, 21.8%). No differences were detected between the two groups. Median follow-up time was significantly longer in patients <65 than ≥65 years. We observed 41 (9.5%) cancer-related death events. The death rate was similar between the two age groups. However, the Kaplan Meier curve showed a longer survival time for younger patients compared to older patients [HR 2.5 (CI 95%: 1.27–4.94), p < 0.01]. Nevertheless, no differences in the aggressiveness of the disease at presentation and in the number and type of treatments performed were found in the two subgroups of dead patients. In patients with sporadic MTC, age at diagnosis did not correlate with any clinical and pathological features. Cancer-related death events are similar in older and younger patients, but survival time is longer in the younger. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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36. Further Clarification of Pain Management Complexity in Radiotherapy: Insights from Modern Statistical Approaches
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Costanza Maria Donati, Erika Galietta, Francesco Cellini, Alessia Di Rito, Maurizio Portaluri, Cristina De Tommaso, Anna Santacaterina, Consuelo Tamburella, Filippo Mammini, Rossella Di Franco, Salvatore Parisi, Sabrina Cossa, Antonella Bianculli, Pierpaolo Ziccarelli, Luigi Ziccarelli, Domenico Genovesi, Luciana Caravatta, Francesco Deodato, Gabriella Macchia, Francesco Fiorica, Giuseppe Napoli, Silvia Cammelli, Letizia Cavallini, Milly Buwenge, Romina Rossi, Marco Maltoni, Alessio Giuseppe Morganti, and Savino Cilla
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observational study ,multicenter ,radiotherapy ,pain ,pain management index ,least absolute shrinkage and selection operator (LASSO) algorithm ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: The primary objective of this study was to assess the adequacy of analgesic care in radiotherapy (RT) patients, with a secondary objective to identify predictive variables associated with pain management adequacy using a modern statistical approach, integrating the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and the Classification and Regression Tree (CART) analysis. Methods: This observational, multicenter cohort study involved 1387 patients reporting pain or taking analgesic drugs from 13 RT departments in Italy. The Pain Management Index (PMI) served as the measure for pain control adequacy, with a PMI score < 0 indicating suboptimal management. Patient demographics, clinical status, and treatment-related factors were examined to discern the predictors of pain management adequacy. Results: Among the analyzed cohort, 46.1% reported inadequately managed pain. Non-cancer pain origin, breast cancer diagnosis, higher ECOG Performance Status scores, younger patient age, early assessment phase, and curative treatment intent emerged as significant determinants of negative PMI from the LASSO analysis. Notably, pain management was observed to improve as RT progressed, with a greater discrepancy between cancer (33.2% with PMI < 0) and non-cancer pain (73.1% with PMI < 0). Breast cancer patients under 70 years of age with non-cancer pain had the highest rate of negative PMI at 86.5%, highlighting a potential deficiency in managing benign pain in younger patients. Conclusions: The study underscores the dynamic nature of pain management during RT, suggesting improvements over the treatment course yet revealing specific challenges in non-cancer pain management, particularly among younger breast cancer patients. The use of advanced statistical techniques for analysis stresses the importance of a multifaceted approach to pain management, one that incorporates both cancer and non-cancer pain considerations to ensure a holistic and improved quality of oncological care.
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- 2024
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37. Adequacy of Pain Management in Patients Referred for Radiation Therapy: A Subanalysis of the Multicenter ARISE-1 Study
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Costanza M. Donati, Chiara Maria Maggiore, Marco Maltoni, Romina Rossi, Elena Nardi, Alice Zamagni, Giambattista Siepe, Filippo Mammini, Francesco Cellini, Alessia Di Rito, Maurizio Portaluri, Cristina De Tommaso, Anna Santacaterina, Consuelo Tamburella, Rossella Di Franco, Salvatore Parisi, Sabrina Cossa, Vincenzo Fusco, Antonella Bianculli, Pierpaolo Ziccarelli, Luigi Ziccarelli, Domenico Genovesi, Luciana Caravatta, Francesco Deodato, Gabriella Macchia, Francesco Fiorica, Giuseppe Napoli, Milly Buwenge, and Alessio G. Morganti
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pain management ,cancer patients ,radiotherapy ,pain management index ,modified pain management index ,palliative care ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Pain is a prevalent symptom among cancer patients, and its management is crucial for improving their quality of life. However, pain management in cancer patients referred to radiotherapy (RT) departments is often inadequate, and limited research has been conducted on this specific population. This study aimed to assess the adequacy and effectiveness of pain management when patients are referred for RT. Moreover, we explored potential predictors of adequate pain management. Methods: This observational, prospective, multicenter cohort study included cancer patients aged 18 years or older who were referred to RT departments. A pain management assessment was conducted using the Pain Management Index (PMI), calculated by subtracting the pain score from the analgesic score (PMI < 0 indicated inadequate pain management). Univariate and multivariate analyses were performed to identify predictors of adequate pain management. Results: A total of 1042 cancer outpatients were included in the study. The analysis revealed that 42.9% of patients with pain did not receive adequate pain management based on PMI values. Among patients with pain or taking analgesics and referred to palliative or curative RT, 72% and 75% had inadequate or ineffective analgesic therapy, respectively. The odds of receiving adequate pain management (PMI ≥ 0) were higher in patients undergoing palliative RT (OR 2.52; p < 0.001), with worse ECOG-PS scores of 2, 3 and 4 (OR 1.63, 2.23, 5.31, respectively; p: 0.017, 0.002, 0.009, respectively) compared to a score of 1 for those with cancer-related pain (OR 0.38; p < 0.001), and treated in northern Italy compared to central and southern of Italy (OR 0.25, 0.42, respectively; p < 0.001). Conclusions: In this study, a substantial proportion of cancer patients referred to RT departments did not receive adequate pain management. Educational and organizational strategies are necessary to address the inadequate pain management observed in this population. Moreover, increasing the attention paid to non-cancer pain and an earlier referral of patients for palliative RT in the course of the disease may improve pain response and treatment outcomes.
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- 2023
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38. Analysis of Health-Related Quality of Life Reporting in Phase III RCTs of Advanced Genitourinary Tumors
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Fabrizio Di Costanzo, Fabiana Napolitano, Fabio Salomone, Anna Rita Amato, Gennaro Alberico, Fortuna Migliaccio, Giovanna Pecoraro, Annachiara Marra, Felice Crocetto, Antonio Ruffo, Sarah Scagliarini, Sabrina Rossetti, Livio Puglia, Marilena Di Napoli, Roberto Bianco, Alberto Servetto, and Luigi Formisano
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genitourinary cancers ,health-related quality of life ,patient-reported outcomes ,CONSORT-PRO ,randomized controlled trials ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: As recommended in the European Society for Medical Oncology (ESMO) guidelines, assessment of health-related quality of life (HRQoL) should be a relevant endpoint in randomized controlled trials (RCTs) testing new anticancer therapies. However, previous publications by our group and others revealed a frequent underestimation and underreporting of HRQoL results in publication of RCTs in oncology. Herein, we systematically reviewed HRQoL reporting in RCTs testing new treatments in advanced prostate, kidney and urothelial cancers and published between 2010 and 2022. Methods: We searched PubMed RCTs testing novel therapies in genitourinary (GU) cancers and published in fifteen selected journals (Annals of Oncology, BMC Cancer, British Journal of Cancer, Cancer Discovery, Clinical Cancer Research, Clinical Genitourinary cancer, European Journal of Cancer, European Urology, European Urology Oncology, JAMA, JAMA Oncology, Journal of clinical Oncology, Lancet, Lancet Oncology and The New England Journal of Medicine). We excluded trials investigating exclusively best supportive care or behavioral intervention, as well as subgroup or post hoc analyses of previously published trials. For each RCT, we investigated whether HRQoL assessment was performed by protocol and if results were reported in the primary manuscript or in a secondary publication. Results: We found 85 eligible trials published between 2010 and 2022. Only 1/85 RCTs (1.2%) included HRQoL among primary endpoints. Of note, 25/85 (29.4%) RCTs did not include HRQoL among study endpoints. HRQoL results were non-disclosed in 56/85 (65.9%) primary publications. Only 18/85 (21.2%) publications fulfilled at least one item of the CONSORT-PRO checklist. Furthermore, 14/46 (30.4%) RCTs in prostate cancer, 12/25 (48%) in kidney cancer and 3/14 (21.4%) in urothelial cancer reported HRQoL data in primary publications. Next, HRQoL data were disclosed in primary manuscripts of 12/32 (37.5%), 5/13 (38.5%), 5/16 (31.3%) and 5/15 (33.3%) trials evaluating target therapies, chemotherapy, immunotherapy and new hormonal agents, respectively. Next, we found that HRQoL data were reported in 16/42 (38%) and in 13/43 (30.2%) positive and negative trials, respectively. Finally, the rate of RCTs reporting HRQoL results in primary or secondary publications was 55.3% (n = 47/85). Conclusions: Our analysis revealed a relevant underreporting of HRQoL in RCTs in advanced GU cancers. These results highlight the need to dedicate more attention to HRQoL in RCTs to fully assess the value of new anticancer treatments.
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- 2023
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39. Exploring the Potential of Non-Coding RNAs as Liquid Biopsy Biomarkers for Lung Cancer Screening: A Literature Review
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Edoardo Garbo, Benedetta Del Rio, Giorgia Ferrari, Massimiliano Cani, Valerio Maria Napoli, Valentina Bertaglia, Enrica Capelletto, Christian Rolfo, Silvia Novello, and Francesco Passiglia
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lung cancer ,screening ,liquid biopsy ,non-coding RNA ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Lung cancer represent the leading cause of cancer mortality, so several efforts have been focused on the development of a screening program. To address the issue of high overdiagnosis and false positive rates associated to LDCT-based screening, there is a need for new diagnostic biomarkers, with liquid biopsy ncRNAs detection emerging as a promising approach. In this scenario, this work provides an updated summary of the literature evidence about the role of non-coding RNAs in lung cancer screening. A literature search on PubMed was performed including studies which investigated liquid biopsy non-coding RNAs biomarker lung cancer patients and a control cohort. Micro RNAs were the most widely studied biomarkers in this setting but some preliminary evidence was found also for other non-coding RNAs, suggesting that a multi-biomarker based liquid biopsy approach could enhance their efficacy in the screening context. However, further studies are needed in order to optimize detection techniques as well as diagnostic accuracy before introducing novel biomarkers in the early diagnosis setting.
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- 2023
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40. Serum Paraprotein Is Associated with Adverse Prognostic Factors and Outcome, across Different Subtypes of Mature B-Cell Malignancies—A Systematic Review
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Maria Christina Cox, Fabiana Esposito, Massimiliano Postorino, Adriano Venditti, and Arianna Di Napoli
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non-Hodgkin lymphoma ,NHL ,diffuse large B-cell lymphoma ,follicular lymphoma ,marginal-zone lymphoma ,MALT ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The presence of a serum paraprotein (PP) is usually associated with plasma-cell dyscrasias, Waldenstrom Macroglobulinemia/lymphoplasmacytic lymphoma, and cryoglobulinemia. However, PP is also often reported in other high- and low-grade B-cell malignancies. As these reports are sparse and heterogeneous, an overall view on this topic is lacking, Therefore, we carried out a complete literature review to detail the characteristics, and highlight differences and similarities among lymphoma entities associated with PP. In these settings, IgM and IgG are the prevalent PP subtypes, and their serum concentration is often low or even undetectable without immunofixation. The relevance of paraproteinemia and its prevalence, as well as the impact of IgG vs. IgM PP, seems to differ within B-NHL subtypes and CLL. Nonetheless, paraproteinemia is almost always associated with advanced disease, as well as with immunophenotypic, genetic, and clinical features, impacting prognosis. In fact, PP is reported as an independent prognostic marker of poor outcome. All the above call for implementing clinical practice, with the assessment of paraproteinemia, in patients’ work-up. Indeed, more studies are needed to shed light on the biological mechanism causing more aggressive disease. Furthermore, the significance of paraproteinemia, in the era of targeted therapies, should be assessed in prospective trials.
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- 2023
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41. DICER1 Syndrome: A Multicenter Surgical Experience and Systematic Review
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Claudio Spinelli, Marco Ghionzoli, Linda Idrissi Sahli, Carla Guglielmo, Silvia Frascella, Silvia Romano, Carlo Ferrari, Fabrizio Gennari, Giovanni Conzo, Riccardo Morganti, Luigi De Napoli, Lucia Quaglietta, Lucia De Martino, Stefania Picariello, Anna Grandone, Caterina Luongo, Antonella Gambale, Armando Patrizio, Poupak Fallahi, Alessandro Antonelli, and Silvia Martina Ferrari
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DICER1 ,neoplasms ,genetic mutation ,surgery ,children ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
DICER1 syndrome is a rare genetic disorder that predisposes patients to the development of malignant and non-malignant diseases. Presently, DICER1 syndrome diagnosis still occurs late, usually following surgical operations, affecting patients’ outcomes, especially for further neoplasms, which are entailed in this syndrome. For this reason, herein we present a multicenter report of DICER1 syndrome, with the prospective aim of enhancing post-surgical surveillance. A cohort of seven patients was collected among the surgical registries of Pediatric Surgery at the University of Pisa with the General and Oncologic Surgery of Federico II, University of Naples, and the Pediatric Surgery, Regina Margherita Hospital, University of Turin. In each case, the following data were analyzed: sex, age at diagnosis, age at first surgery, clinical features, familial, genetic investigations, and follow-up. A comprehensive literature review of DICER1 cases, including case reports and multicenter studies published from 1996 to June 2022, was performed. Eventually, the retrieved data from the literature were compared with the data emerging from our cohort of patients.
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- 2023
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42. Genetic Ablation of the MET Oncogene Defines a Crucial Role of the HGF/MET Axis in Cell-Autonomous Functions Driving Tumor Dissemination
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Chiara Modica, Marco Cortese, Francesca Bersani, Andrea Maria Lombardi, Francesca Napoli, Luisella Righi, Riccardo Taulli, Cristina Basilico, and Elisa Vigna
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metastasis ,invasion ,MET ,HGF ,pancreatic cancers ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Cancer cell dissemination is sustained by cell-autonomous and non-cell-autonomous functions. To disentangle the role of HGF (Hepatocyte Growth Factor) and MET ligand/receptor axis in this complex process, we genetically knocked out the MET gene in cancer cells in which MET is not the oncogenic driver. In this way, we evaluated the contribution of the HGF/MET axis to cancer cell dissemination independently of its direct activities in cells of the tumor microenvironment. The lack of MET expression in MET−/− cells has been proved by molecular characterization. From a functional point of view, HGF stimulation of MET−/− cancer cells was ineffective in eliciting intracellular signaling and in sustaining biological functions predictive of malignancy in vitro (i.e., anchorage-independent growth, invasion, and survival in the absence of matrix adhesion). Cancer cell dissemination was assessed in vivo, evaluating: (i) the ability of MET−/− lung carcinoma cells to colonize the lungs following intravenous injection and (ii) the spontaneous dissemination to distant organs of MET−/− pancreatic carcinoma cells upon orthotopic injection. In both experimental models, MET ablation affects the time of onset, the number, and the size of metastatic lesions. These results define a crucial contribution of the HGF/MET axis to cell-autonomous functions driving the metastatic process.
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- 2023
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43. Safety of Inhomogeneous Dose Distribution IMRT for High-Grade Glioma Reirradiation: A Prospective Phase I/II Trial (GLIORAD TRIAL)
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Patrizia Ciammella, Salvatore Cozzi, Andrea Botti, Lucia Giaccherini, Roberto Sghedoni, Matteo Orlandi, Manuela Napoli, Rosario Pascarella, Anna Pisanello, Marco Russo, Francesco Cavallieri, Maria Paola Ruggieri, Silvio Cavuto, Luisa Savoldi, Cinzia Iotti, and Mauro Iori
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glioblastoma multiforme ,GBM ,re-irradiation ,recurrence ,recurrent GBM ,voxel-based dose escalation ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Glioblastoma multiforme (GBM) is the most aggressive astrocytic primary brain tumor, and concurrent temozolomide (TMZ) and radiotherapy (RT) followed by maintenance of adjuvant TMZ is the current standard of care. Despite advances in imaging techniques and multi-modal treatment options, the median overall survival (OS) remains poor. As an alternative to surgery, re-irradiation (re-RT) can be a therapeutic option in recurrent GBM. Re-irradiation for brain tumors is increasingly used today, and several studies have demonstrated its feasibility. Besides differing techniques, the published data include a wide range of doses, emphasizing that no standard approach exists. The current study aimed to investigate the safety of moderate–high-voxel-based dose escalation in recurrent GBM. From 2016 to 2019, 12 patients met the inclusion criteria and were enrolled in this prospective single-center study. Retreatment consisted of re-irradiation with a total dose of 30 Gy (up to 50 Gy) over 5 days using the IMRT (arc VMAT) technique. A dose painting by numbers (DPBN)/dose escalation plan were performed, and a continuous relation between the voxel intensity of the functional image set and the risk of recurrence in that voxel were used to define target and dose distribution. Re-irradiation was well tolerated in all treated patients. No toxicities greater than G3 were recorded; only one patient had severe G3 acute toxicity, characterized by muscle weakness and fatigue. Median overall survival (OS2) and progression-free survival (PFS2) from the time of re-irradiation were 10.4 months and 5.7 months, respectively; 3-, 6-, and 12-month OS2 were 92%, 75%, and 42%, respectively; and 3-, 6-, and 12-month PFS2 were 83%, 42%, and 8%, respectively. Our work demonstrated a tolerable tolerance profile of this approach, and the future prospective phase II study will analyze the efficacy in terms of PFS and OS.
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- 2022
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44. Prostate Cancer and Sleep Disorders: A Systematic Review
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Davide Sparasci, Ilenia Napoli, Lorenzo Rossi, Ricardo Pereira-Mestre, Mauro Manconi, Giorgio Treglia, Laura Marandino, Margaret Ottaviano, Fabio Turco, Dylan Mangan, Silke Gillessen, and Ursula Maria Vogl
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systematic review ,sleep disorder ,prostate cancer ,androgen deprivation therapy ,radiotherapy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Prostate cancer (PCa) treatment involves multiple strategies depending on the disease’s stage. Androgen deprivation therapy (ADT) remains the gold standard for advanced and metastatic stages. Sleep quality has been suggested as being additionally influenced also by local radiotherapy, prostatectomy and androgen-receptor (AR)-targeted agents. We performed a systematic review exploring the landscape of studies published between 1 January 1990 and 31 July 2021, investigating sleep disturbances in PCa patients receiving active treatments, including the influence of hormonal therapy on sleep quality as a factor affecting their quality of life. Out of 45 articles identified, 16 studies were selected, which recruited patients with PCa, undergoing active treatment in either a prospective longitudinal or cross-sectional study. Development of sleep disorders or changes in sleep quality were reported in 14 out of 16 trials included. Only five trials included objective measurements such as actigraphy, mostly at one time point and without a baseline assessment. Limitations to be addressed are the small number of existing trials, lack of randomized trials and heterogeneity of methodologies used. This systematic review outlines the lack of prospective trials investigating sleep disorders, with a rigorous methodology, in homogeneous cohorts of PCa patients. Future trials are needed to clarify the prevalence and impact of this side effect of PCa treatments.
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- 2022
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45. RNA Sequencing of Primary Cutaneous and Breast-Implant Associated Anaplastic Large Cell Lymphomas Reveals Infrequent Fusion Transcripts and Upregulation of PI3K/AKT Signaling via Neurotrophin Pathway Genes
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Arianna Di Napoli, Davide Vacca, Giorgio Bertolazzi, Gianluca Lopez, Maria Piane, Aldo Germani, Evelina Rogges, Giuseppina Pepe, Fabio Santanelli Di Pompeo, Marzia Salgarello, Vaidehi Jobanputra, Susan Hsiao, Kazimierz O. Wrzeszczynski, Emilio Berti, and Govind Bhagat
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ALCL ,fusion transcripts ,transcriptome ,PI3K/Akt pathway ,NTRK signaling ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Cutaneous and breast implant-associated anaplastic large-cell lymphomas (cALCLs and BI-ALCLs) are two localized forms of peripheral T-cell lymphomas (PTCLs) that are recognized as distinct entities within the family of ALCL. JAK-STAT signaling is a common feature of all ALCL subtypes, whereas DUSP22/IRF4, TP63 and TYK gene rearrangements have been reported in a proportion of ALK-negative sALCLs and cALCLs. Both cALCLs and BI-ALCLs differ in their gene expression profiles compared to PTCLs; however, a direct comparison of the genomic alterations and transcriptomes of these two entities is lacking. By performing RNA sequencing of 1385 genes (TruSight RNA Pan-Cancer, Illumina) in 12 cALCLs, 10 BI-ALCLs and two anaplastic lymphoma kinase (ALK)-positive sALCLs, we identified the previously reported TYK2-NPM1 fusion in 1 cALCL (1/12, 8%), and four new intrachromosomal gene fusions in 2 BI-ALCLs (2/10, 20%) involving genes on chromosome 1 (EPS15-GNG12 and ARNT-GOLPH3L) and on chromosome 17 (MYO18A-GIT1 and NF1-GOSR1). One of the two BI-ALCL samples showed a complex karyotype, raising the possibility that genomic instability may be responsible for intra-chromosomal fusions in BI-ALCL. Moreover, transcriptional analysis revealed similar upregulation of the PI3K/Akt pathway, associated with enrichment in the expression of neurotrophin signaling genes, which was more conspicuous in BI-ALCL, as well as differences, i.e., over-expression of genes involved in the RNA polymerase II transcription program in BI-ALCL and of the RNA splicing/processing program in cALCL.
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- 2021
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46. Targeting KRAS in NSCLC: Old Failures and New Options for 'Non-G12c' Patients
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Francesca Jacobs, Massimiliano Cani, Umberto Malapelle, Silvia Novello, Valerio Maria Napoli, and Paolo Bironzo
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KRAS ,G12C ,oncogene ,non-G12C ,targeted therapy ,NSCLC ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) gene mutations are among the most common driver alterations in non-small cell lung cancer (NSCLC). Despite their high frequency, valid treatment options are still lacking, mainly due to an intrinsic complexity of both the protein structure and the downstream pathway. The increasing knowledge about different mutation subtypes and co-mutations has paved the way to several promising therapeutic strategies. Despite the best results so far having been obtained in patients harbouring KRAS exon 2 p.G12C mutation, even the treatment landscape of non-p.G12C KRAS mutation positive patients is predicted to change soon. This review provides a comprehensive and critical overview of ongoing studies into NSCLC patients with KRAS mutations other than p.G12C and discusses future scenarios that will hopefully change the story of this disease.
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- 2021
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47. Cardiac Toxicity Associated with Cancer Immunotherapy and Biological Drugs
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Andrea Montisci, Maria Teresa Vietri, Vittorio Palmieri, Silvia Sala, Francesco Donatelli, and Claudio Napoli
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cancer ,immunotherapy ,myocarditis ,trastuzumab ,chimeric antigen receptor-modified T (CAR-T) ,immune checkpoint inhibitors ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Cancer immunotherapy significantly contributed to an improvement in the prognosis of cancer patients. Immunotherapy, including human epidermal growth factor receptor 2 (HER2)-targeted therapies, immune checkpoint inhibitors (ICI), and chimeric antigen receptor-modified T (CAR-T), share the characteristic to exploit the capabilities of the immune system to kill cancerous cells. Trastuzumab is a monoclonal antibody against HER2 that prevents HER2-mediated signaling; it is administered mainly in HER2-positive cancers, such as breast, colorectal, biliary tract, and non-small-cell lung cancers. Immune checkpoint inhibitors (ICI) inhibit the binding of CTLA-4 or PD-1 to PDL-1, allowing T cells to kill cancerous cells. ICI can be used in melanomas, non-small-cell lung cancer, urothelial, and head and neck cancer. There are two main types of T-cell transfer therapy: tumor-infiltrating lymphocytes (or TIL) therapy and chimeric antigen receptor-modified T (CAR-T) cell therapy, mainly applied for B-cell lymphoma and leukemia and mantle-cell lymphoma. HER2-targeted therapies, mainly trastuzumab, are associated with left ventricular dysfunction, usually reversible and rarely life-threatening. PD/PDL-1 inhibitors can cause myocarditis, rare but potentially fulminant and associated with a high fatality rate. CAR-T therapy is associated with several cardiac toxic effects, mainly in the context of a systemic adverse effect, the cytokines release syndrome.
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- 2021
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48. Evaluation of the Preclinical Efficacy of Lurbinectedin in Malignant Pleural Mesothelioma
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Dario P. Anobile, Paolo Bironzo, Francesca Picca, Marcello F. Lingua, Deborah Morena, Luisella Righi, Francesca Napoli, Mauro G. Papotti, Alessandra Pittaro, Federica Di Nicolantonio, Chiara Gigliotti, Federico Bussolino, Valentina Comunanza, Francesco Guerrera, Alberto Sandri, Francesco Leo, Roberta Libener, Pablo Aviles, Silvia Novello, Riccardo Taulli, Giorgio V. Scagliotti, and Chiara Riganti
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MPM ,lurbinectedin ,DNA damage response ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Malignant pleural mesothelioma (MPM) is a highly aggressive cancer generally diagnosed at an advanced stage and characterized by a poor prognosis. The absence of alterations in druggable kinases, together with an immune-suppressive tumor microenvironment, limits the use of molecular targeted therapies, making the treatment of MPM particularly challenging. Here we investigated the in vitro susceptibility of MPM to lurbinectedin (PM01183), a marine-derived drug that recently received accelerated approval by the FDA for the treatment of patients with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy. Methods: A panel of primary MPM cultures, resembling the three major MPM histological subtypes (epithelioid, sarcomatoid, and biphasic), was characterized in terms of BAP1 status and histological markers. Subsequently, we explored the effects of lurbinectedin at nanomolar concentration on cell cycle, cell viability, DNA damage, genotoxic stress response, and proliferation. Results: Stabilized MPM cultures exhibited high sensitivity to lurbinectedin independently from the BAP1 mutational status and histological classification. Specifically, we observed that lurbinectedin rapidly promoted a cell cycle arrest in the S-phase and the activation of the DNA damage response, two conditions that invariably resulted in an irreversible DNA fragmentation, together with strong apoptotic cell death. Moreover, the analysis of long-term treatment indicated that lurbinectedin severely impacts MPM transforming abilities in vitro. Conclusion: Overall, our data provide evidence that lurbinectedin exerts a potent antitumoral activity on primary MPM cells, independently from both the histological subtype and BAP1 alteration, suggesting its potential activity in the treatment of MPM patients.
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- 2021
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49. Beyond Abscopal Effect: A Meta-Analysis of Immune Checkpoint Inhibitors and Radiotherapy in Advanced Non-Small Cell Lung Cancer
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Francesco Fiorica, Umberto Tebano, Milena Gabbani, Mariasole Perrone, Sonia Missiroli, Massimiliano Berretta, Jacopo Giuliani, Andrea Bonetti, Andrea Remo, Eva Pigozzi, Andrea Tontini, Giuseppe Napoli, Nicoletta Luca, Daniela Grigolato, Paolo Pinton, and Carlotta Giorgi
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combination of immune checkpoint inhibitors and radiotherapy ,radiation oncology and immunity ,radiation oncology ,immunotherapy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Immune checkpoint inhibitors (ICI) plus radiotherapy (RT) have been suggested as an emerging combination in non-small cell lung cancer (NSCLC) patients. However, little is known about the magnitude of its benefits and potential clinical predictors. Objective: To assess the effects of this combination on the increase in overall and progression-free survival. Data sources: The MEDLINE and CANCERLIT (1970–2020) electronic databases were searched, and the reference lists of included studies were manually searched. Study selection: Studies were included if they were comparative studies between combination ICI-RT and ICI or RT alone in advanced or metastatic NSCLC patients. Overall survival (OS) was analyzed according to the treatment strategy. Data extraction: Data on population, intervention, and outcomes were extracted from each study, in accordance with the intention-to-treat method, by two independent observers and combined using the DerSimonian method and Laird method. Results: Compared to ICI or RT alone, ICI-RT significantly increased the 1-year and 3-year OS RR by 0.75 (95% CI 0.64–0.88; p = 0.0003) and 0.85 (95% CI 0.78–0.93; p = 0.0006), respectively. Furthermore, there was a statistically significant benefit on 1- and 3-year progression-free survival (RR 0.73 (95% CI, 0.61–0.87; p = 0.0005) and RR 0.82 (95% CI 0.67–0.99; p = 0.04), respectively). Conclusions: In patients with advanced or metastatic NSCLC, combination ICI-RT increases 1- and 3-year OS and progression-free survival compared to ICI or RT alone.
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- 2021
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50. Pathological Characterization of Tumor Immune Microenvironment (TIME) in Malignant Pleural Mesothelioma
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Francesca Napoli, Angela Listì, Vanessa Zambelli, Gianluca Witel, Paolo Bironzo, Mauro Papotti, Marco Volante, Giorgio Scagliotti, and Luisella Righi
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mesothelioma ,tumor microenvironment ,tumor-associated macrophages ,dendritic cells ,immunohistochemistry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Malignant pleural mesothelioma (MPM) is a rare and highly aggressive disease that arises from pleural mesothelial cells, characterized by a median survival of approximately 13–15 months after diagnosis. The primary cause of this disease is asbestos exposure and the main issues associated with it are late diagnosis and lack of effective therapies. Asbestos-induced cellular damage is associated with the generation of an inflammatory microenvironment that influences and supports tumor growth, possibly in association with patients’ genetic predisposition and tumor genomic profile. The chronic inflammatory response to asbestos fibers leads to a unique tumor immune microenvironment (TIME) composed of a heterogeneous mixture of stromal, endothelial, and immune cells, and relative composition and interaction among them is suggested to bear prognostic and therapeutic implications. TIME in MPM is known to be constituted by immunosuppressive cells, such as type 2 tumor-associated macrophages and T regulatory lymphocytes, plus the expression of several immunosuppressive factors, such as tumor-associated PD-L1. Several studies in recent years have contributed to achieve a greater understanding of the pathogenetic mechanisms in tumor development and pathobiology of TIME, that opens the way to new therapeutic strategies. The study of TIME is fundamental in identifying appropriate prognostic and predictive tissue biomarkers. In the present review, we summarize the current knowledge about the pathological characterization of TIME in MPM.
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- 2021
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