63 results on '"Antonino Grassadonia"'
Search Results
2. Optimizing the Choice for Adjuvant Chemotherapy in Gastric Cancer
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Antonino Grassadonia, Antonella De Luca, Erminia Carletti, Patrizia Vici, Francesca Sofia Di Lisa, Lorena Filomeno, Giuseppe Cicero, Laura De Lellis, Serena Veschi, Rosalba Florio, Davide Brocco, Saverio Alberti, Alessandro Cama, Nicola Tinari, and Antonino Grassadonia, Antonella De Luca, Erminia Carletti, Patrizia Vici, Francesca Sofia Di Lisa, Lorena Filomeno, Giuseppe Cicero, Laura De Lellis, Serena Veschi, Rosalba Florio, Davide Brocco, Saverio Alberti, Alessandro Cama, Nicola Tinari
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adjuvant chemotherapy ,predictive factor ,Cancer Research ,Oncology ,gastric cancer ,prognostic factors - Abstract
Advances in the management of gastric cancer have improved patient survival in the last decade. Nonetheless, the number of patients relapsing and dying after a diagnosis of localized gastric cancer is still too high, even in early stages (10% in stage I). Adjuvant systemic chemotherapy has been proven to significantly improve outcomes. In the present article we have critically reviewed the clinical trials that guide the current clinical practice in the adjuvant treatment of patients affected by resectable gastric cancer, focusing on the different approaches worldwide, i.e., adjuvant chemotherapy, adjuvant chemoradiotherapy, and perioperative chemotherapy. We also delineate the clinical–pathological characteristics that are commonly taken into account to identify patients at a higher risk of recurrence and requiring adjuvant chemotherapy, and also describe novel biomarkers and therapeutic agents that might allow personalization of the treatment.
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- 2022
3. The Impact of the Hippo Pathway and Cell Metabolism on Pathological Complete Response in Locally Advanced Her2+ Breast Cancer: The TRISKELE Multicenter Prospective Study
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Eriseld Krasniqi, Francesca Sofia Di Lisa, Anna Di Benedetto, Maddalena Barba, Laura Pizzuti, Lorena Filomeno, Cristiana Ercolani, Nicola Tinari, Antonino Grassadonia, Daniele Santini, Mauro Minelli, Filippo Montemurro, Maria Agnese Fabbri, Marco Mazzotta, Teresa Gamucci, Giuliana D’Auria, Claudio Botti, Fabio Pelle, Flavia Cavicchi, Sonia Cappelli, Federico Cappuzzo, Giuseppe Sanguineti, Silverio Tomao, Andrea Botticelli, Paolo Marchetti, Marcello Maugeri-Saccà, Ruggero De Maria, Gennaro Ciliberto, Francesca Sperati, and Patrizia Vici
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Cancer Research ,Hippo pathway ,cell metabolism ,Her2−positive breast cancer ,pathological complete response ,Oncology - Abstract
The Hippo pathway and its two key effectors, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), are consistently altered in breast cancer. Pivotal regulators of cell metabolism such as the AMP-activated protein kinase (AMPK), Stearoyl-CoA-desaturase 1 (SCD1), and HMG-CoA reductase (HMGCR) are relevant modulators of TAZ/YAP activity. In this prospective study, we measured the tumor expression of TAZ, YAP, AMPK, SCD1, and HMGCR by immunohistochemistry in 65 Her2+ breast cancer patients who underwent trastuzumab-based neoadjuvant treatment. The aim of the study was to assess the impact of the immunohistochemical expression of the Hippo pathway transducers and cell metabolism regulators on pathological complete response. Low expression of cytoplasmic TAZ, both alone and in the context of a composite signature identified by machine learning including also low nuclear levels of YAP and HMGCR and high cytoplasmic levels of SCD1, was a predictor of residual disease in the univariate logistic regression. This finding was not confirmed in the multivariate model including estrogen receptor > 70% and body mass index > 20. However, our findings were concordant with overall survival data from the TCGA cohort. Our results, possibly affected by the relatively small sample size of this study population, deserve further investigation in adequately sized, ad hoc prospective studies.
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- 2022
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4. MicroRNA-based signatures impacting clinical course and biology of ovarian cancer: a miRNOmics study
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L. Pizzuti, Giovanni Blandino, Eriseld Krasniqi, Lorenza Landi, Maddalena Barba, Andrea Sacconi, Teresa Gamucci, Silverio Tomao, A. Bagnato, Domenico Sergi, M. De Tursi, S. Donzelli, Daniele Marinelli, Gennaro Ciliberto, Piero Marchetti, Marco Mazzotta, N. Tinari, Federico Cappuzzo, Mariantonia Carosi, Patrizia Vici, Clara Natoli, Enrico Vizza, Antonino Grassadonia, and E. Capomolla
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Clinical Biochemistry ,Disease ,RM1-950 ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Ovarian cancer ,Platinum resistance ,Internal medicine ,microRNA ,medicine ,Research ,ovarian cancer ,prognostic/predictive biomarkers ,miRNAs ,Biochemistry (medical) ,Clinical course ,Cancer ,Prognostic/predictive biomarkers ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cohort ,Molecular Medicine ,Therapeutics. Pharmacology - Abstract
Background In Western countries, ovarian cancer (OC) still represents the leading cause of gynecological cancer-related deaths, despite the remarkable gains in therapeutical options. Novel biomarkers of early diagnosis, prognosis definition and prediction of treatment outcomes are of pivotal importance. Prior studies have shown the potentials of micro-ribonucleic acids (miRNAs) as biomarkers for OC and other cancers. Methods We focused on the prognostic and/or predictive potential of miRNAs in OC by conducting a comprehensive array profiling of miRNA expression levels in ovarian tissue samples from 17 non-neoplastic controls, and 60 tumor samples from OC patients treated at the Regina Elena National Cancer Institute (IRE). A set of 54 miRNAs with differential expression in tumor versus normal samples (T/N-deregulated) was identified in the IRE cohort and validated against data from the Cancer Genoma Atlas (TCGA) related to 563 OC patients and 8 non-neoplastic controls. The prognostic/predictive role of the selected 54 biomarkers was tested in reference to survival endpoints and platinum resistance (P-res). Results In the IRE cohort, downregulation of the 2 miRNA-signature including miR-99a-5p and miR-320a held a negative prognostic relevance, while upregulation of miR-224-5p was predictive of less favorable event free survival (EFS) and P-res. Data from the TCGA showed that downregulation of 5 miRNAs, i.e., miR-150, miR-30d, miR-342, miR-424, and miR-502, was associated with more favorable EFS and overall survival outcomes, while miR-200a upregulation was predictive of P-res. The 9 miRNAs globally identified were all included into a single biologic signature, which was tested in enrichment analysis using predicted/validated miRNA target genes, followed by network representation of the miRNA-mRNA interactions. Conclusions Specific dysregulated microRNA sets in tumor tissue showed predictive/prognostic value in OC, and resulted in a promising biological signature for this disease.
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- 2021
5. High Blood Concentration of Leukocyte-Derived Extracellular Vesicles Is Predictive of Favorable Clinical Outcomes in Patients with Pancreatic Cancer: Results from a Multicenter Prospective Study
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Davide Brocco, Domenico De Bellis, Pietro Di Marino, Pasquale Simeone, Antonino Grassadonia, Michele De Tursi, Tommaso Grottola, Fabio Francesco Di Mola, Patrizia Di Gregorio, Barbara Zappacosta, Antonio Angelone, Laura De Lellis, Serena Veschi, Rosalba Florio, Simone De Fabritiis, Fabio Verginelli, Marco Marchisio, Marta Caporale, Dimitri Luisi, Pierluigi Di Sebastiano, Nicola Tinari, Alessandro Cama, and Paola Lanuti
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Cancer Research ,pancreatic cancer ,leukocytes ,extracellular vesicles ,Oncology - Abstract
Pancreatic cancer (PC) is one of the leading causes of cancer-related death worldwide. Identification of novel tumor biomarkers is highly advocated in PC to optimize personalized treatment algorithms. Blood-circulating extracellular vesicles hold promise for liquid biopsy application in cancer. We used an optimized flow cytometry protocol to study leukocyte-derived EVs (CD45+) and PD-L1+ EVs in blood from 56 pancreatic cancer patients and 48 healthy controls (HCs). Our results show that PC patients presented higher blood levels of total EVs (p = 0.0003), leukocyte-derived EVs (LEVs) (p = 0.001) and PD-L1+ EVs (p = 0.01), as compared with HCs. Interestingly, a blood concentration of LEVs at baseline was independently associated with improved overall survival in patients with borderline resectable or primary unresectable PC (HR = 0.17; 95% CI 0.04–0.79; p = 0.02). Additionally, increased blood-based LEVs were independently correlated with prolonged progression-free survival (HR = 0.10; 95% CI 0.01–0.82; p = 0.03) and significantly associated with higher disease control rate (p = 0.02) in patients with advanced PC receiving standard chemotherapy. Notably, a strong correlation between a decrease in blood LEVs concentration during chemotherapy and disease control was observed (p = 0.005). These intriguing findings point to the potential of LEVs as novel blood-based EV biomarkers for improved personalized medicine in patients affected by PC.
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- 2022
6. Blood Circulating CD133+ Extracellular Vesicles Predict Clinical Outcomes in Patients with Metastatic Colorectal Cancer
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Davide Brocco, Pasquale Simeone, Davide Buca, Pietro Di Marino, Michele De Tursi, Antonino Grassadonia, Laura De Lellis, Maria Teresa Martino, Serena Veschi, Manuela Iezzi, Simone De Fabritiis, Marco Marchisio, Sebastiano Miscia, Alessandro Cama, Paola Lanuti, and Nicola Tinari
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Cancer Research ,extracellular vesicles ,circulating biomarkers ,colorectal cancer ,Oncology ,digestive system diseases - Abstract
Colorectal cancer (CRC) is one of the most incident and lethal malignancies worldwide. Recent treatment advances prolonged survival in patients with metastatic colorectal cancer (mCRC). However, there are still few biomarkers to guide clinical management and treatment selection in mCRC. In this study, we applied an optimized flow cytometry protocol for EV identification, enumeration, and subtyping in blood samples of 54 patients with mCRC and 48 age and sex-matched healthy controls (HCs). The overall survival (OS) and overall response rate (ORR) were evaluated in mCRC patients enrolled and treated with a first line fluoropyrimidine-based regimen. Our findings show that patients with mCRC presented considerably higher blood concentrations of total EVs, as well as CD133+ and EPCAM+ EVs compared to HCs. Overall survival analysis revealed that increased blood concentrations of total EVs and CD133+ EVs before treatment were significantly associated with shorter OS in mCRC patients (p = 0.001; and p = 0.0001, respectively). In addition, we observed a correlation between high blood levels of CD133+ EVs at baseline and reduced ORR to first-line systemic therapy (p = 0.045). These findings may open exciting perspectives into the application of novel blood-based EV biomarkers for improved risk stratification and optimized treatment strategies in mCRC.
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- 2022
7. Predictive Ability for Disease-Free Survival of the GRade, Age, Nodes, and Tumor (GRANT) Score in Patients with Resected Renal Cell Carcinoma
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Giampiero Porzio, Luca Cindolo, Alessio Cortellini, Melissa Bersanelli, Corrado Ficorella, Giada Pinterpe, Lucilla Verna, Antonino Grassadonia, Olga Venditti, Katia Cannita, Michele De Tursi, Luigi Di Clemente, Clara Natoli, Sebastiano Buti, and Nicola Tinari
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Original Paper ,medicine.medical_specialty ,education.field_of_study ,Disease free survival ,Multivariate analysis ,business.industry ,Urology ,Population ,Retrospective cohort study ,medicine.disease ,Oncology ,Reproductive Medicine ,Renal cell carcinoma ,Internal medicine ,medicine ,Population study ,In patient ,education ,business ,Pathological - Abstract
BACKGROUND: Recently, the GRANT (GRade, Age, Nodes, and Tumor) score was validated through an adjuvant trial population. METHODS: This retrospective study evaluated the performance of the GRANT score as a prognostic model for disease-free survival (DFS), compared to the University of California Los Angeles Integrated Staging System (UISS) score, in a “real-life” population of early renal cell carcinoma patients. A uni-/multivariate analysis of DFS was also performed, to weigh the roles of baseline clinical factors. RESULTS: From February 1998 to January 2018, 134 consecutive patients were enrolled, of which 85 patients (63.4%) had a favorable GRANT score, 49 (36.6%) an unfavorable GRANT score, and 21 (15.7%), 84 (62.6%), and 29 (21.6%) patients had a low, intermediate, or high risk of recurrence according to the UISS score, respectively. The median follow-up was 96 months. The median DFS of the overall study population was 53.7 months (95% CI: 38.4-87.8). Only bilateral renal cell carcinoma (p = 0.0041), Fuhrman grade 3/4 (p = 0.0008), pT3b- 4 (p = 0.0324), and pN1-2 (p = 0.0303) pathological status were confirmed as independent predictors of a shorter DFS by the multivariate analysis. The median DFS of patients with favorable and unfavorable GRANT scores were 84.9 (95% CI: 49.8-129) and 38.4 months (95% CI: 24.4-87.8), respectively, with a statistically significant difference (p = 0.0147). The median DFS of patients with low, intermediate, and high risk of recurrence according to the UISS score were 92.3 (95% CI: 18.1-153.9), 51.7 (95% CI: 36.2-87.8), and 49.8 months (95% CI: 31.3-129), respectively, without statistically significant differences (p = 0.4728). DFS c-statistic values were 0.59 (95% CI: 0.51-0.67) and 0.51 (95% CI: 0.42-0.60) for the GRANT and the UISS scores, respectively. CONCLUSION: The GRANT score might be a useful tool that is user-friendly and easy to perform in clinical practice.
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- 2020
8. Whole breast radiotherapy in cN0 early breast cancer patients with pathological sentinel lymph nodes (pN1mic, pN1a) without axillary dissection: preliminary results of the observational LISEN trial
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Lucia Anna Ursini, Marianna Nuzzo, Consuelo Rosa, Marzia Borgia, Luciana Caravatta, Monica Di Tommaso, Marianna Trignani, Fiorella Cristina Di Guglielmo, Giampiero Ausili Cefaro, Domenico Angelucci, Marzia Muzi, Gianluigi Martino, Ettore Cianchetti, Simona Grossi, Saveria Tavoletta, Davide Brocco, Antonino Grassadonia, Nicola Tinari, Simona Gildetti, Nicola D’Ostilio, Liborio Stuppia, Annamaria Porreca, Marta Di Nicola, and Domenico Genovesi
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Male ,Oncology ,Sentinel Lymph Node Biopsy ,Lymphatic Metastasis ,Axilla ,Humans ,Lymph Node Excision ,Radiology, Nuclear Medicine and imaging ,Breast Neoplasms ,Female ,Lymph Nodes ,Sentinel Lymph Node - Abstract
Purpose Axillary management remains unclear when sentinel lymph node (SLN) results are positive in cN0 patients with breast cancer (BC). The trial ACOSOG Z0011 represented a revolution with axillary lymph node dissection (ALND) omission in SLN+ patients, despite critiques regarding non-uniformity of radiation fields. We conducted an observational study (LISEN) where whole breast radiotherapy (WBRT) was planned with tangential fields without nodal irradiation in patients eligible for the Z0011 trial. Methods Inclusion criteria were female patients with histologically proven BC, cT1-2cN0, planned conservative surgery, no neoadjuvant therapy. Patients were stratified into two groups: micrometastatic (pN1mic, group 1) and macrometastatic (pN1a, group 2) lymph nodes. Tangential field WBRT was mandatory. Clinical outcomes were analysed, measured from surgery until the first event. Results In all, 199 patients underwent conservative surgery and SLN biopsy; 133 patients meeting criteria were analysed: 41 patients (30.8%) pN1mic and 92 (69.2%) pN1a. The 5‑year disease-free survival (DFS) was 95.0% (85.9–100%) in group 1 and 93.0% (86.3–100.0%) in group 2 (p = 0.78). Overall survival (OS) was 100% (100–100%) in group 1 and 97.4% (92.4–100%) in group 2 (p = 0.74). For the whole cohort DFS and OS were 93.6% (88.2–99.4%) and 96.9% (91.5–100.0%), respectively. For groups 1 and 2, the 5‑year outcomes were 5.0% (0.0–14.4%) and 2.3% (0.0–6.1%) for local recurrence (p = 0.51), and 6.2% (0.0–17.4%) and 7.0% (0.0–13.7%) for distant metastasis (p = 0.61), respectively. In group 1, regional recurrence (RR) and local regional recurrence (LRR) were 5.0% (0.0–14.1%; p = 0.13). In group 2, RR and LRR were 0.0% (0.0–0.0%). Conclusion Our results showed good regional control in patients who met the Z0011 trial criteria. WBRT, without nodal surgery or RT, avoiding axillary morbidity, seems to be a good choice.
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- 2021
9. PANHER study: a 20-year treatment outcome analysis from a multicentre observational study of HER2-positive advanced breast cancer patients from the real-world setting
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Angela Maione, Nicola Tinari, Paola Pinnarò, Enzo Maria Ruggeri, Isabella Sperduti, Olivia Bacciu, Emanuela Risi, Icro Meattini, Federica Tomao, Luca Marchetti, Nicola D’Ostilio, Patrizia Vici, Lorenza Landi, Giuseppina Sarobba, Lucia Mentuccia, Elisabetta Landucci, Emilio Bria, A.F. Scinto, Gennaro Ciliberto, Laura Pizzuti, Elena Fiorio, Andrea Michelotti, Ida Paris, Simonetta Stani, Antonio Russo, Clara Natoli, Rosa Saltarelli, Alessandra Cassano, Paolo Marchetti, Maria Agnese Fabbri, Daniele Marinelli, Ferdinando Riccardi, Mauro Minelli, Corrado Ficorella, Anna Ceribelli, Maria Rosaria Valerio, Maddalena Barba, Jennifer Foglietta, Maria Mauri, Teresa Gamucci, Luca Moscetti, Beatrice Taurelli Salimbeni, Fabio Pelle, Daniele Santini, Andrea Botticelli, Vito Lorusso, Mirco Pistelli, Giacomo Barchiesi, Francesco Giotta, Eriseld Krasniqi, Antonino Grassadonia, Simone Scagnoli, Valentina Sini, Katia Cannita, Flavia Cavicchi, Michele De Tursi, Mimma Raffaele, Marco Mazzotta, Sonia Cappelli, Paola Scavina, Francesca Sofia Di Lisa, Giuliana D’Auria, Armando Orlandi, Marcello Maugeri-Saccà, Federico Cappuzzo, Claudio Botti, Nello Salesi, Lorenzo Livi, Beatrice Fratini, Giulia Bon, Silverio Tomao, Giuseppe Sanguineti, Enzo Veltri, Domenico Corsi, Enrico Cortesi, Rossana Berardi, Laura Iezzi, Rosalinda Rossi, Giuseppe Tonini, Elisabetta Maria Capomolla, Pizzuti L., Krasniqi E., Sperduti I., Barba M., Gamucci T., Mauri M., Veltri E.M., Meattini I., Berardi R., Di Lisa F.S., Natoli C., Pistelli M., Iezzi L., Risi E., D'Ostilio N., Tomao S., Ficorella C., Cannita K., Riccardi F., Cassano A., Bria E., Fabbri M.A., Mazzotta M., Barchiesi G., Botticelli A., D'Auria G., Ceribelli A., Michelotti A., Russo A., Salimbeni B.T., Sarobba G., Giotta F., Paris I., Saltarelli R., Marinelli D., Corsi D., Capomolla E.M., Sini V., Moscetti L., Mentuccia L., Tonini G., Raffaele M., Marchetti L., Minelli M., Ruggeri E.M., Scavina P., Bacciu O., Salesi N., Livi L., Tinari N., Grassadonia A., Fedele Scinto A., Rossi R., Valerio M.R., Landucci E., Stani S., Fratini B., Maugeri-Sacca M., De Tursi M., Maione A., Santini D., Orlandi A., Lorusso V., Cortesi E., Sanguineti G., Pinnaro P., Cappuzzo F., Landi L., Botti C., Tomao F., Cappelli S., Bon G., Pelle F., Cavicchi F., Fiorio E., Foglietta J., Scagnoli S., Marchetti P., Ciliberto G., and Vici P.
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Oncology ,medicine.medical_specialty ,Advanced breast ,T-DM1 ,Treatment outcome ,Lapatinib ,Breast cancer ,pertuzumab ,Internal medicine ,Medicine ,lapatinib ,RC254-282 ,advanced breast cancer ,business.industry ,Human epidermal growth factor ,HER2-positive ,sequence ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Cancer ,medicine.disease ,Observational study ,Pertuzumab ,business ,medicine.drug - Abstract
Background: The evolution of therapeutic landscape of human epidermal growth factor receptor-2 (HER2)-positive breast cancer (BC) has led to an unprecedented outcome improvement, even if the optimal sequence strategy is still debated. To address this issue and to provide a picture of the advancement of anti-HER2 treatments, we performed a large, multicenter, retrospective study of HER2-positive BC patients. Methods: The observational PANHER study included 1,328 HER2-positive advanced BC patients treated with HER2 blocking agents since June 2000 throughout July 2020. Endpoints of efficacy were progression-free survival (PFS) and overall survival (OS). Results: Patients who received a first-line pertuzumab-based regimen showed better PFS ( p < 0.0001) and OS ( p = 0.004) than those receiving other treatments. Median PFS and mOS from second-line starting were 8 and 28 months, without significant differences among various regimens. Pertuzumab-pretreated patients showed a mPFS and a mOS from second-line starting not significantly affected by type of second line, that is, T-DM1 or lapatinib/capecitabine ( p = 0.80 and p = 0.45, respectively). Conversely, pertuzumab-naïve patients receiving second-line T-DM1 showed a significantly higher mPFS compared with that of patients treated with lapatinib/capecitabine ( p = 0.004). Median OS from metastatic disease diagnosis was higher in patients treated with trastuzumab-based first line followed by second-line T-DM1 in comparison to pertuzumab-based first-line and second-line T-DM1 ( p = 0.003), although these data might be partially influenced by more favorable prognostic characteristics of patients in the pre-pertuzumab era. No significant differences emerged when comparing patients treated with ‘old’ or ‘new’ drugs ( p = 0.43), even though differences in the length of the follow-up between the two cohorts should be taken into account. Conclusion: Our results confirmed a relevant impact of first-line pertuzumab-based treatment and showed lower efficacy of second-line T-DM1 in trastuzumab/pertuzumab pretreated, as compared with pertuzumab-naïve patients. Our findings may help delineate a more appropriate therapeutic strategy in HER2-positive metastatic BC. Prospective randomized trials addressing this topic are awaited.
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- 2021
10. Drug Repurposing, an Attractive Strategy in Pancreatic Cancer Treatment: Preclinical and Clinical Updates
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Nicola Tinari, Zhirajr Mokini, Davide Brocco, Alessandro Cama, Serena Veschi, Laura De Lellis, Simone Carradori, Rosalba Florio, and Antonino Grassadonia
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0301 basic medicine ,Drug ,Cancer Research ,Pancreatic ductal adenocarcinoma ,media_common.quotation_subject ,pancreatic ductal adenocarcinoma ,Disease ,Review ,drug repositioning ,Bioinformatics ,immunomodulation ,03 medical and health sciences ,0302 clinical medicine ,Pancreatic cancer ,Medicine ,tumor microenvironment ,Repurposing ,RC254-282 ,media_common ,business.industry ,repurposed drugs ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Preclinical data ,Drug repositioning ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Molecular targets ,business - Abstract
Simple Summary The purpose of this review is to provide an update on some of the most promising non-oncology drugs that are already approved and that could be useful also in the treatment of pancreatic cancer, one of the deadliest malignancies worldwide. Current chemotherapy options are unsatisfactory in this cancer and there is an urgent need for more effective and less toxic drugs to improve the dismal pancreatic cancer therapy. The use in cancer therapy of drugs approved for other indications (drug repurposing) is an attractive approach that has the potential to overcome several issues associated with de novo drug discovery, such as dose-finding and safety profiles, accelerating their clinical adoption. In this review, we report proposed mechanisms of action and biological targets of drugs that are candidates for repurposing in pancreatic cancer therapy, focusing on targets that appear to be relevant for their anticancer action. Finally, considering that cancer immunotherapy provides remarkable long-term remission in some responsive tumors and that this strategy is mostly ineffective in pancreatic cancer patients, we discuss recent developments regarding the ability of some repurposing drug candidates to activate anti-tumor immune response, which may be particularly relevant for their clinical effectiveness. Abstract Pancreatic cancer (PC) is one of the deadliest malignancies worldwide, since patients rarely display symptoms until an advanced and unresectable stage of the disease. Current chemotherapy options are unsatisfactory and there is an urgent need for more effective and less toxic drugs to improve the dismal PC therapy. Repurposing of non-oncology drugs in PC treatment represents a very promising therapeutic option and different compounds are currently being considered as candidates for repurposing in the treatment of this tumor. In this review, we provide an update on some of the most promising FDA-approved, non-oncology, repurposed drug candidates that show prominent clinical and preclinical data in pancreatic cancer. We also focus on proposed mechanisms of action and known molecular targets that they modulate in PC. Furthermore, we provide an explorative bioinformatic analysis, which suggests that some of the PC repurposed drug candidates have additional, unexplored, oncology-relevant targets. Finally, we discuss recent developments regarding the immunomodulatory role displayed by some of these drugs, which may expand their potential application in synergy with approved anticancer immunomodulatory agents that are mostly ineffective as single agents in PC.
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- 2021
11. Prognostic Relevance of Neutrophil to Lymphocyte Ratio (NLR) in Luminal Breast Cancer: A Retrospective Analysis in the Neoadjuvant Setting
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Marco Mazzotta, Nicola Tinari, Eriseld Krasniqi, Laura Iezzi, A. Amodio, Clara Natoli, Laura Pizzuti, Giuseppe Cicero, Maddalena Barba, Vincenzo Graziano, Patrizia Vici, Antonino Grassadonia, Daniele Marinelli, Grassadonia A., Graziano V., Iezzi L., Vici P., Barba M., Pizzuti L., Cicero G., Krasniqi E., Mazzotta M., Marinelli D., Amodio A., Natoli C., Tinari N., Graziano, Vincenzo [0000-0001-7656-824X], and Apollo - University of Cambridge Repository
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0301 basic medicine ,Oncology ,Adult ,medicine.medical_specialty ,Multivariate analysis ,Neutrophils ,QH301-705.5 ,medicine.medical_treatment ,Breast Neoplasms ,Article ,Disease-Free Survival ,predictive/prognostic biomarkers ,03 medical and health sciences ,0302 clinical medicine ,Text mining ,Breast cancer ,luminal breast cancer ,Internal medicine ,Medicine ,Humans ,Lymphocytes ,Neutrophil to lymphocyte ratio ,Biology (General) ,Neoadjuvant therapy ,Aged ,Retrospective Studies ,Chemotherapy ,business.industry ,Proportional hazards model ,allergology ,fungi ,Luminal breast cancer ,Neoadjuvant chemotherapy ,Neutrophil to lymphocyte ratio (NLR) ,Predictive/prognostic biomarkers ,Female ,Ki-67 Antigen ,Middle Aged ,Multivariate Analysis ,Prognosis ,Treatment Outcome ,Neoadjuvant Therapy ,Histology ,General Medicine ,medicine.disease ,neutrophil to lymphocyte ratio (NLR) ,030104 developmental biology ,030220 oncology & carcinogenesis ,Population study ,business ,neoadjuvant chemotherapy - Abstract
The neutrophil to lymphocyte ratio (NLR) is a promising predictive and prognostic factor in breast cancer. We investigated its ability to predict disease-free survival (DFS) and overall survival (OS) in patients with luminal A- or luminal B-HER2-negative breast cancer who received neoadjuvant chemotherapy (NACT). Pre-treatment complete blood cell counts from 168 consecutive patients with luminal breast cancer were evaluated to assess NLR. The study population was stratified into NLRlow or NLRhigh according to a cut-off value established by receiving operator curve (ROC) analysis. Data on additional pre- and post-treatment clinical-pathological characteristics were also collected. Kaplan–Meier curves, log-rank tests, and Cox proportional hazards models were used for statistical analyses. Patients with pre-treatment NLRlow showed a significantly shorter DFS (HR: 6.97, 95% CI: 1.65–10.55, p = 0.002) and OS (HR: 7.79, 95% CI: 1.25–15.07, p = 0.021) compared to those with NLRhigh. Non-ductal histology, luminal B subtype, and post-treatment Ki67 ≥ 14% were also associated with worse DFS (p = 0.016, p = 0.002, and p = 0.001, respectively). In a multivariate analysis, luminal B subtype, post-treatment Ki67 ≥ 14%, and NLRlow remained independent prognostic factors for DFS, while only post-treatment Ki67 ≥ 14% and NLRlow affected OS. The present study provides evidence that pre-treatment NLRlow helps identify women at higher risk of recurrence and death among patients affected by luminal breast cancer treated with NACT.
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- 2021
12. A Case of Stage I Vulvar Squamous Cell Carcinoma with Early Relapse and Rapid Disease Progression
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Marinella Zilli, Marta Peri, Patrizia Vici, Michele De Tursi, Clara Natoli, Antonino Grassadonia, Laura Iezzi, and Nicola Tinari
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Oncology ,medicine.medical_specialty ,Vulvar Squamous Cell Carcinoma ,Early Relapse ,Case Report ,Disease ,lcsh:RC254-282 ,Stage ib ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Stage (cooking) ,neoplasms ,030219 obstetrics & reproductive medicine ,business.industry ,Vulvar cancer ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Rapid disease progression ,female genital diseases and pregnancy complications ,stomatognathic diseases ,Tumor progression ,030220 oncology & carcinogenesis ,business - Abstract
Squamous cell carcinoma (SCC) is the most common subtype of vulvar cancer. Locoregional surgery is often curative when the tumor is diagnosed at an early stage. However, the disease can unexpectedly evolve with a dismal prognosis even after an early diagnosis. We report a case of a woman who experienced a rapid, chemorefractory tumor progression after surgery for stage IB vulvar SCC.
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- 2019
13. Eribulin in Triple Negative Metastatic Breast Cancer: Critic Interpretation of Current Evidence and Projection for Future Scenarios
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Maddalena Barba, Silverio Tomao, Gioia Massimiani, Marco Mazzotta, Gennaro Ciliberto, Teresa Gamucci, Aldo Venuti, Giacomo Barchiesi, Patrizia Vici, Giuseppe Sanguineti, Eriseld Krasniqi, Ramy Kayal, Fabio Pelle, Laura Pizzuti, Paolo Marchetti, Clara Natoli, Enrico Vizza, Antonino Grassadonia, and A. Amodio
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Receptor expression ,Review ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,triple negative subtype ,Internal medicine ,medicine ,eribulin ,Triple-negative breast cancer ,Chemotherapy ,business.industry ,Immunotherapy ,medicine.disease ,Metastatic breast cancer ,Clinical trial ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,Observational study ,metastatic breast cancer ,business ,Eribulin - Abstract
Triple negative breast cancer (TNBC) is characterized by distinctive biological features that confer an aggressive clinical behavior. In TNBC patients, the absence of well-defined driver pathways such as hormonal receptor expression or hyperactivation of the human epidermal growth factor receptor 2 (HER2) significantly reduce the spectrum of therapeutic options, which are currently mainly confined to chemotherapy. Thus far, median overall survival for patients with metastatic TNBC is about 9-12 months with conventional cytotoxic agents. However, the heterogeneity recently revealed at a gene expression level inside the TNBC family may help inform therapeutic decisions concerning the use of chemotherapy and hopefully lead the way to novel targeted options that include immunotherapy. Eribulin, a halichondrin class antineoplastic drug, is currently recommended for treatment of HER2 negative metastatic or recurrent breast cancer (BC) previously exposed to anthracyclines and taxanes, also for patients with a TNBC. It is currently indicated from the second line of treatment. In this review, we aim to analyze a wide range of cumulated evidence on eribulin use in TNBC including preclinical studies, intervention and observational clinical trials. Data from the real-world setting and the emerging evidence increasingly substantiating the rationale for combinations with new generation treatment strategies, e.g., PARP-inhibitors, immune checkpoint inhibitors, will be also discussed.
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- 2019
14. Phenotypic and Proteomic Analysis Identifies Hallmarks of Blood Circulating Extracellular Vesicles in NSCLC Responders to Immune Checkpoint Inhibitors
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Luca Federici, Sebastiano Miscia, Nicola Tinari, Damiana Pieragostino, Pietro Di Marino, Luciana Irtelli, Rosalba Florio, Marco Marchisio, Antonino Grassadonia, Pasquale Simeone, Laura De Lellis, Paola Lanuti, Michele De Tursi, Maria Concetta Cufaro, Piero Del Boccio, Alessandro Cama, Serena Veschi, Giuseppina Bologna, and Davide Brocco
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0301 basic medicine ,Cancer Research ,medicine.medical_treatment ,lcsh:RC254-282 ,Article ,Flow cytometry ,immune checkpoint inhibitors ,03 medical and health sciences ,0302 clinical medicine ,Cancer immunotherapy ,medicine ,Shotgun proteomics ,non-small cell lung cancer ,Chemotherapy ,cancer immunotherapy ,medicine.diagnostic_test ,business.industry ,Immunotherapy ,Extracellular vesicle ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Proteome ,Cancer research ,Biomarker (medicine) ,biomarker ,business ,extracellular vesicles - Abstract
Simple Summary Purpose of this study was to investigate the prognostic and predictive role of blood circulating extracellular vesicles (EVs) in patients with advanced non-small cell lung cancer treated with immunotherapy. A newly optimized flow cytometry protocol was applied for identification and subtyping of blood circulating EVs in a total cohort of 59 NSCLC patients, which included 31 patients treated with anti-PD-1/PD-L1 agents and 28 patients treated with traditional chemotherapy. Our results show that pre-treatment concentration of blood circulating endothelial-derived EVs was correlated with overall survival and clinical response in patients treated with immunotherapy. Additionally, proteomic analysis of purified blood circulating EVs indicated differences in EV protein cargo between responders and non-responders to immunotherapy. These findings may pave the way to the identification of novel immunotherapy biomarkers in patients with advanced NSCLC. Abstract Immune checkpoint inhibitors (ICIs) induce durable clinical responses only in a subset of advanced non-small cell lung cancer (NSCLC) patients. There is a need to identify mechanisms of ICI resistance and immunotherapy biomarkers to improve clinical benefit. In this study, we evaluated the prognostic and predictive value of circulating endothelial and leukocyte-derived extracellular vesicles (EV) in patients with advanced NSCLC treated with anti-PD-1/PD-L1 agents. In addition, the relationship between total blood circulating EV proteome and response to ICIs was investigated. An optimized flow cytometry method was employed for the identification and subtyping of blood circulating EVs in 59 patients with advanced NSCLC. Blood samples were collected from patients receiving anti-PD-1/PD-L1 inhibitors (n = 31) or chemotherapy (n = 28). An exploratory proteomic analysis of sorted blood EVs was conducted in a subset of patients. Our results show that a low blood concentration of circulating endothelial-derived EVs before treatment was strongly associated to longer overall survival (p = 0.0004) and higher disease control rate (p = 0.045) in patients treated with ICIs. Interestingly, shotgun proteomics revealed that EVs of responders to anti-PD-1 therapy had a specific protein cargo before treatment. In addition, EV protein cargo was specifically modulated during immunotherapy. We identified a previously unknown association between circulating endothelial-derived extracellular vesicle concentration and immunotherapy-related clinical outcomes. We also observed differences in circulating extracellular vesicle proteome according to anti-PD-1-based treatment response in NSCLC patients. Overall, these results may contribute to the identification of novel circulating biomarkers for rational immunotherapy approaches in patients affected by NSCLC.
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- 2021
15. Differential influence of antibiotic therapy and other medications on oncological outcomes of patients with non-small cell lung cancer treated with first-line pembrolizumab versus cytotoxic chemotherapy
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Gabriele Minuti, Serena Ricciardi, Rita Chiari, Giovanni Mansueto, Francesco Grossi, Alessandro De Toma, Olga Nigro, Luigi Della Gravara, Alessandro Russo, Lorenza Landi, Alessandro Inno, Alessandro Leonetti, Annalisa Guida, Miriam Grazia Ferrara, Francesca Mazzoni, Marco Siringo, Paola Bordi, Paolo Bironzo, Erika Rijavec, De Tursi Michele, Massimo Di Maio, Francesco Passiglia, Gian Paolo Spinelli, Paolo Marchetti, Alessio Cortellini, Marco Filetti, Diego Signorelli, Fabrizio Citarella, Fausto Barbieri, Alfredo Addeo, Francesca Rastelli, Vincenzo Sforza, Emilio Bria, Corrado Ficorella, Alessandro Tuzi, Giulio Metro, Pietro Di Marino, Marina Chiara Garassino, David J. Pinato, Alain Gelibter, Alex Friedlaender, Daniele Santini, Joachim G.J.V. Aerts, Mariangela Torniai, Ettore D'Argento, Rossana Berardi, Giuseppe Luigi Banna, Antonino Grassadonia, Marianna Macerelli, Marco Russano, Luca Cantini, Federica Zoratto, Katia Cannita, Maria Rita Migliorino, Carlo Genova, Danilo Rocco, Giampiero Porzio, Vincenzo Adamo, Diego Cortinovis, Raffaele Giusti, Giorgia Guaitoli, and Pulmonary Medicine
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0301 basic medicine ,Oncology ,Male ,Cancer Research ,Time Factors ,medicine.medical_treatment ,Pembrolizumab ,0302 clinical medicine ,Adrenal Cortex Hormones ,Risk Factors ,Carcinoma, Non-Small-Cell Lung ,Monoclonal ,Antineoplastic Combined Chemotherapy Protocols ,80 and over ,Immunology and Allergy ,Non-Small-Cell Lung ,Humanized ,Immune Checkpoint Inhibitors ,RC254-282 ,Aged, 80 and over ,Clinical/Translational Cancer Immunotherapy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Middle Aged ,immunotherapy ,lung neoplasms ,Adult ,Aged ,Anti-Bacterial Agents ,Antibodies, Monoclonal, Humanized ,Europe ,Female ,Humans ,Lung Neoplasms ,Polypharmacy ,Progression-Free Survival ,Proton Pump Inhibitors ,Retrospective Studies ,Risk Assessment ,030220 oncology & carcinogenesis ,Cohort ,Molecular Medicine ,medicine.medical_specialty ,Immunology ,Antibodies ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Internal medicine ,medicine ,Progression-free survival ,Lung cancer ,Pharmacology ,Chemotherapy ,Performance status ,business.industry ,Carcinoma ,Retrospective cohort study ,medicine.disease ,030104 developmental biology ,Concomitant ,business - Abstract
BackgroundSome concomitant medications including antibiotics (ATB) have been reproducibly associated with worse survival following immune checkpoint inhibitors (ICIs) in unselected patients with non-small cell lung cancer (NSCLC) (according to programmed death-ligand 1 (PD-L1) expression and treatment line). Whether such relationship is causative or associative is matter of debate.MethodsWe present the outcomes analysis according to concomitant baseline medications (prior to ICI initiation) with putative immune-modulatory effects in a large cohort of patients with metastatic NSCLC with a PD-L1 expression ≥50%, receiving first-line pembrolizumab monotherapy. We also evaluated a control cohort of patients with metastatic NSCLC treated with first-line chemotherapy. The interaction between key medications and therapeutic modality (pembrolizumab vs chemotherapy) was validated in pooled multivariable analyses.Results950 and 595 patients were included in the pembrolizumab and chemotherapy cohorts, respectively. Corticosteroid and proton pump inhibitor (PPI) therapy but not ATB therapy was associated with poorer performance status at baseline in both the cohorts. No association with clinical outcomes was found according to baseline statin, aspirin, β-blocker and metformin within the pembrolizumab cohort. On the multivariable analysis, ATB emerged as a strong predictor of worse overall survival (OS) (HR=1.42 (95% CI 1.13 to 1.79); p=0.0024), and progression free survival (PFS) (HR=1.29 (95% CI 1.04 to 1.59); p=0.0192) in the pembrolizumab but not in the chemotherapy cohort. Corticosteroids were associated with shorter PFS (HR=1.69 (95% CI 1.42 to 2.03); pConclusionIn this study, we validate the significant negative impact of ATB on pembrolizumab monotherapy but not chemotherapy outcomes in NSCLC, producing further evidence about their underlying immune-modulatory effect. Even though the magnitude of the impact of corticosteroids and PPIs is significantly different across the cohorts, their effects might be driven by adverse disease features.
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- 2021
16. Metronomic chemotherapy (mCHT) in metastatic triple-negative breast cancer (TNBC) patients: results of the VICTOR-6 study
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Katia Cagossi, A. Ferzi, Domenico Amoroso, A. Baldelli, Luca Clivio, Mariangela Ciccarese, Viola Cogliati, Ornella Garrone, P. Spadaro, Daniele Santini, Vita Leonardi, Elisabetta Cretella, Luca Gianni, A. Gambaro, Alfredo Butera, A. Turletti, M.G. Sarobba, Giovanni Scognamiglio, Vittorio Gebbia, Cristiana Taverniti, F. Ferraù, D. Toniolo, Saverio Cinieri, C. Putzu, S. Capici, Antonino Musolino, Daniele Generali, Paolo Tralongo, Marina Elena Cazzaniga, Valter Torri, Antonino Grassadonia, Andrea Fontana, Emilia Montagna, E. de Conciliis, P. Di Mauro, Maria Rosaria Valerio, Rossana Berardi, Silvana Saracchini, Ferdinando Riccardi, Antonio Febbraro, I. Vallini, Patrizia Vici, Luigi Cavanna, M. G. Schintu, Roberto Valenza, F. Giovanardi, M. Nicolini, Samanta Sarti, Paolo Marchetti, Cazzaniga, M, Vallini, I, Montagna, E, Amoroso, D, Berardi, R, Butera, A, Cagossi, K, Cavanna, L, Ciccarese, M, Cinieri, S, Cretella, E, De Conciliis, E, Febbraro, A, Ferrau, F, Ferzi, A, Baldelli, A, Fontana, A, Gambaro, A, Garrone, O, Gebbia, V, Generali, D, Gianni, L, Giovanardi, F, Grassadonia, A, Leonardi, V, Marchetti, P, Sarti, S, Musolino, A, Nicolini, M, Putzu, C, Riccardi, F, Santini, D, Saracchini, S, Sarobba, M, Schintu, M, Scognamiglio, G, Spadaro, P, Taverniti, C, Toniolo, D, Tralongo, P, Turletti, A, Valenza, R, Valerio, M, Vici, P, Di Mauro, P, Cogliati, V, Capici, S, Clivio, L, Torri, V, Cazzaniga, M. E., Vallini, I., Montagna, E., Amoroso, D., Berardi, R., Butera, A., Cagossi, K., Cavanna, L., Ciccarese, M., Cinieri, S., Cretella, E., De Conciliis, E., Febbraro, A., Ferrau, F., Ferzi, A., Baldelli, A., Fontana, A., Gambaro, A. R., Garrone, O., Gebbia, V., Generali, D., Gianni, L., Giovanardi, F., Grassadonia, A., Leonardi, V., Marchetti, P., Sarti, S., Musolino, A., Nicolini, M., Putzu, C., Riccardi, F., Santini, D., Saracchini, S., Sarobba, M. G., Schintu, M. G., Scognamiglio, G., Spadaro, P., Taverniti, C., Toniolo, D., Tralongo, P., Turletti, A., Valenza, R., Valerio, M. R., Vici, P., Clivio, L., Torri, V., Cazzaniga, M E, Ferraù, F, Gambaro, A R, Sarobba, M G, Schintu, M G, and Valerio, M R
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Oncology ,Cancer Research ,medicine.medical_specialty ,Receptor, ErbB-2 ,Breast Neoplasms ,Triple Negative Breast Neoplasms ,Vinorelbine ,Capecitabine ,Cyclophosphamide ,Methotrexate ,Metronomic chemotherapy ,Triple-negative breast cancer ,Antineoplastic Combined Chemotherapy Protocols ,Female ,Humans ,Retrospective Studies ,ErbB-2 ,Breast cancer ,Retrospective Studie ,Internal medicine ,medicine ,Progression-free survival ,Antineoplastic Combined Chemotherapy Protocol ,business.industry ,medicine.disease ,Clinical Trial ,Metronomic Chemotherapy ,Metastatic breast cancer ,Regimen ,business ,Breast Neoplasm ,Human ,Receptor ,medicine.drug - Abstract
Purpose Triple-negative breast cancer (TNBC) represents a subtype of breast cancer which lacks the expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2): TNBC accounts for approximately 20% of newly diagnosed breast cancers and is associated with younger age at diagnosis, greater recurrence risk and shorter survival time. Therapeutic options are very scarce. Aim of the present analysis is to provide further insights into the clinical activity of metronomic chemotherapy (mCHT), in a real-life setting. Methods We used data included in the VICTOR-6 study for the present analysis. VICTOR-6 is an Italian multicentre retrospective cohort study, which collected data of metastatic breast cancer (MBC) patients who have received mCHT between 2011 and 2016. Amongst the 584 patients included in the study, 97 were triple negative. In 40.2% of the TNBC patients, mCHT was the first chemotherapy treatment, whereas 32.9% had received 2 or more lines of treatment for the metastatic disease. 45.4% out of 97 TNBC patients received a vinorelbine (VRL)-based regimen, which resulted in the most used type of mCHT, followed by cyclophosphamide (CTX)-based regimens (30.9%) and capecitabine (CAPE)-based combinations (22.7%). Results Overall response rate (ORR) and disease control rate (DCR) were 17.5% and 64.9%, respectively. Median progression free survival (PFS) and overall survival (OS) were 6.0 months (95% CI: 4.9–7.2) and 12.1 months (95% CI: 9.6–16.7). Median PFS was 6.9 months for CAPE-based regimens (95% CI: 5.0–18.4), 6.1 months (95% CI: 4.0–8.9) for CTX-based and 5.3 months (95% CI: 4.1–9.5) for VRL-based ones. Median OS was 18.2 months (95% CI: 9.1-NE) for CAPE-based regimens and 11.8 months for VRL- (95% CI: 9.3–16.7 and CTX-based ones (95%CI: 8.7–52.8). Tumour response, PFS and OS decreased proportionally in later lines. Conclusion This analysis represents the largest series of TNBC patients treated with mCHT in a real-life setting and provides further insights into the advantages of using this strategy even in this poor prognosis subpopulation.
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- 2021
17. The prognostic relevance of HER2-positivity gain in metastatic breast cancer in the ChangeHER trial
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Pietro Del Medico, Rossana Berardi, Enzo Veltri, Maria Rosaria Valerio, Alessandra Cassano, Daniele Marinelli, Vito Lorusso, Patrizia Vici, Nicola D’Ostilio, Silverio Tomao, Enrico Cortesi, Nicola Tinari, Emilio Bria, Domenico Sergi, Luca Moscetti, Giuseppe Sanguineti, Teresa Gamucci, Claudio Zamagni, Maddalena Barba, Clara Natoli, Theodora Daralioti, Giancarlo Paoletti, Antonino Grassadonia, Marina Elena Cazzaniga, Icro Meattini, Ornella Garrone, Andrea Michelotti, Giuseppina Sarobba, Nicla La Verde, Laura Pizzuti, Letizia Perracchio, Vincenzo Adamo, Giuseppe Tonini, A. Vaccaro, Francesco Giotta, Corrado Ficorella, Maria Agnese Fabbri, Antonio Russo, Paolo Marchetti, Gennaro Ciliberto, Mirco Pistelli, Rosanna Mirabelli, Marco Mazzotta, Daniele Generali, Marcello Maugeri-Saccà, Mario Roselli, Angelo Di Leo, Anna Di Benedetto, Isabella Sperduti, Ida Paris, Eriseld Krasniqi, Carlo Garufi, Lorenzo Livi, Ruggero De Maria, Andrea Botticelli, Domenico Corsi, Pizzuti, L, Barba, M, Mazzotta, M, Krasniqi, E, Maugeri-Sacca, M, Gamucci, T, Berardi, R, Livi, L, Ficorella, C, Natoli, C, Cortesi, E, Generali, D, La Verde, N, Cassano, A, Bria, E, Moscetti, L, Michelotti, A, Adamo, V, Zamagni, C, Tonini, G, Sergi, D, Marinelli, D, Paoletti, G, Tomao, S, Botticelli, A, Marchetti, P, Tinari, N, Grassadonia, A, Valerio, M, Mirabelli, R, Fabbri, M, D'Ostilio, N, Veltri, E, Corsi, D, Garrone, O, Paris, I, Sarobba, G, Meattini, I, Pistelli, M, Giotta, F, Lorusso, V, Garufi, C, Russo, A, Cazzaniga, M, Del Medico, P, Roselli, M, Vaccaro, A, Perracchio, L, di Benedetto, A, Daralioti, T, Sperduti, I, De Maria, R, Di Leo, A, Sanguineti, G, Ciliberto, G, Vici, P, Pizzuti, Laura, Barba, Maddalena, Mazzotta, Marco, Krasniqi, Eriseld, Maugeri-Saccà, Marcello, Gamucci, Teresa, Berardi, Rossana, Livi, Lorenzo, Ficorella, Corrado, Natoli, Clara, Cortesi, Enrico, Generali, Daniele, La Verde, Nicla, Cassano, Alessandra, Bria, Emilio, Moscetti, Luca, Michelotti, Andrea, Adamo, Vincenzo, Zamagni, Claudio, Tonini, Giuseppe, Sergi, Domenico, Marinelli, Daniele, Paoletti, Giancarlo, Tomao, Silverio, Botticelli, Andrea, Marchetti, Paolo, Tinari, Nicola, Grassadonia, Antonino, Valerio, Maria Rosaria, Mirabelli, Rosanna, Fabbri, Maria Agnese, D’Ostilio, Nicola, Veltri, Enzo, Corsi, Domenico, Garrone, Ornella, Paris, Ida, Sarobba, Giuseppina, Meattini, Icro, Pistelli, Mirco, Giotta, Francesco, Lorusso, Vito, Garufi, Carlo, Russo, Antonio, Cazzaniga, Marina, Del Medico, Pietro, Roselli, Mario, Vaccaro, Angela, Perracchio, Letizia, di Benedetto, Anna, Daralioti, Theodora, Sperduti, Isabella, De Maria, Ruggero, Di Leo, Angelo, Sanguineti, Giuseppe, Ciliberto, Gennaro, Vici, Patrizia, Pizzuti L., Barba M., Mazzotta M., Krasniqi E., Maugeri-Sacca M., Gamucci T., Berardi R., Livi L., Ficorella C., Natoli C., Cortesi E., Generali D., La Verde N., Cassano A., Bria E., Moscetti L., Michelotti A., Adamo V., Zamagni C., Tonini G., Sergi D., Marinelli D., Paoletti G., Tomao S., Botticelli A., Marchetti P., Tinari N., Grassadonia A., Valerio M.R., Mirabelli R., Fabbri M.A., D'Ostilio N., Veltri E., Corsi D., Garrone O., Paris I., Sarobba G., Meattini I., Pistelli M., Giotta F., Lorusso V., Garufi C., Russo A., Cazzaniga M., Del Medico P., Roselli M., Vaccaro A., Perracchio L., di Benedetto A., Daralioti T., Sperduti I., De Maria R., Di Leo A., Sanguineti G., Ciliberto G., and Vici P.
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0301 basic medicine ,Oncology ,Cancer therapy ,Receptor, ErbB-2 ,medicine.medical_treatment ,Ado-Trastuzumab Emtansine ,progesterone receptor ,Settore MED/06 ,0302 clinical medicine ,human epidermal growth factor receptor 2 (HER2) ,Antineoplastic Combined Chemotherapy Protocols ,estrogen ,Neoplasm Metastasis ,skin and connective tissue diseases ,Multidisciplinary ,Brain Neoplasms ,Middle Aged ,Prognosis ,Metastatic breast cancer ,Neoplasm Metastasi ,030220 oncology & carcinogenesis ,Medicine ,Female ,Pertuzumab ,metastatic breast cancer ,Receptors, Progesterone ,Breast Neoplasm ,HER2 positivity ,medicine.drug ,Human ,Adult ,medicine.medical_specialty ,medicine.drug_class ,Science ,trastuzumab-emtansine ,Breast Neoplasms ,cancer ,Article ,Disease-Free Survival ,Brain Neoplasm ,03 medical and health sciences ,Breast cancer ,breast cancer ,Settore MED/04 - PATOLOGIA GENERALE ,pertuzumab ,Internal medicine ,Progesterone receptor ,medicine ,Humans ,neoplasms ,Aged ,Chemotherapy ,Antineoplastic Combined Chemotherapy Protocol ,business.industry ,Cancer ,medicine.disease ,HER2-positive ,oncology ,radiotherapy ,chemotherapy ,HER2 ,Radiation therapy ,030104 developmental biology ,Estrogen ,business ,prognostic relevance - Abstract
Breast cancer (BC) heterogeneity is composite in nature, with a wide variety of factors concurring to define several pathological entities, which differ by clinical presentation, pathologic features, therapy administered, and inherent outcomes1. Additional sources of breast cancer heterogeneity may raise during the disease course. In BC patients whose disease was initially diagnosed in the early stage and subsequently progressed with metastatic involvement of one single or multiple site/s, the molecular characteristics of metastatic lesions do not necessary mimic those of the disease initially diagnosed. A well-depicted molecular landscape is crucial for subtype definition, prognostic evaluation and appropriate therapeutic decisions. Accordingly, current guidelines suggest repeating the immunohistochemical (IHC) assessment in patients with metastatic spread and at least one secondary lesion amenable to biopsy2. Discordance in human epidermal growth factor receptor 2 (HER2) status between the tumor and metastatic lesions is widely acknowledged, and not yet completely unraveled in their biologic meaning and prognostic relevance3–11. The overexpression of HER2 or amplification of the related gene is extensively recognized as a feature associated with more aggressive biological behavior12,13. However, the extent to which changes in HER2 status may affect patients’ prognosis is still a matter of debate14. We herein propose an observational study of HER2-positive metastatic breast cancer (mBC) patients treated with the anti-HER2 targeted agents pertuzumab and/or trastuzumab emtansine (T-DM1). Our research question is whether relevant differences exist in long-term outcomes of patients with concordant HER2 status between the primary tumor and its secondary lesion/s compared to patients whose disease revealed HER2-positivity gain at the IHC assessment of metastatic lesions. In our historical cohorts, we also sought to identify factors associated with HER2-positivity gain at the IHC reassessment, for which an impact on prognosis may be foreseen.
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- 2021
18. Impact of BMI on HER2+ metastatic breast cancer patients treated with pertuzumab and/or trastuzumab emtansine. Real-world evidence
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Aangela Vaccaro, Antonio Giordano, Marina Elena Cazzaniga, Antonio Russo, Maddalena Barba, Emilio Bria, Corrado Ficorella, Claudio Botti, Nicla La Verde, Clara Natoli, Valentina Magri, Loretta D'Onofrio, Carlo Garufi, Ruggero De Maria, Maria Rosaria Valerio, Gennaro Ciliberto, Mario Roselli, A. Fabbri, Emanuela Magnolfi, Giuseppina Rosaria Rita Ricciardi, Patrizia Vici, Alessandra Cassano, Emanuela Risi, Isabella Sperduti, Daniele Generali, Daniele Marinelli, Vito Lorusso, Teresa Gamucci, Lorenzo Livi, Giuseppe Tonini, Antonino Grassadonia, Editta Baldini, Marco Mazzotta, Luca Moscetti, Silverio Tomao, Claudio Zamagni, Silvia Carpano, Ornella Garrone, Icro Meattini, Giuseppe Sanguineti, Eriseld Krasniqi, Lucia Mentuccia, Katia Cannita, Daniele Santini, Rossana Mirabelli, Enzo Veltri, Domenico Sergi, Aandrea Michelotti, Alice Villa, Nicola Tinari, Vincenzo Adamo, A. Botticelli, Ramy Kayal, Mirco Pistelli, Domenico Corsi, Pietro Del Medico, Rossana Berardi, Enrico Cortesi, Giacomo Barchiesi, Alain Gelibter, Ida Paris, Elisa Landucci, Pia Di Stefano, Laura Pizzuti, Paolo Marchetti, Luisa Carbognin, Francesco Giotta, A.F. Scinto, Krasniqi, E, Pizzuti, L, Barchiesi, G, Sergi, D, Carpano, S, Botti, C, Kayal, R, Sanguineti, G, Marchetti, P, Botticelli, A, Marinelli, D, Gamucci, T, Natoli, C, Grassadonia, A, Tinari, N, Tomao, S, Tonini, G, Santini, D, Michelotti, A, Mentuccia, L, Vaccaro, A, Magnolfi, E, Gelibter, A, Magri, V, Cortesi, E, D'Onofrio, L, Cassano, A, Cazzaniga, M, Moscetti, L, Fabbri, A, Scinto, A, Corsi, D, Carbognin, L, Bria, E, La Verde, N, Garufi, C, Di Stefano, P, Mirabelli, R, Veltri, E, Paris, I, Giotta, F, Lorusso, V, Landucci, E, Ficorella, C, Roselli, M, Adamo, V, Ricciardi, G, Russo, A, Valerio, M, Berardi, R, Pistelli, M, Cannita, K, Zamagni, C, Garrone, O, Baldini, E, Livi, L, Meattini, I, Del Medico, P, Generali, D, De Maria, R, Risi, E, Ciliberto, G, Villa, A, Sperduti, I, Mazzotta, M, Barba, M, Giordano, A, Vici, P, Eriseld K., Laura P., Giacomo B., Domenico S., Silvia C., Claudio B., Ramy K., Giuseppe S., Paolo M., Andrea B., Daniele M., Teresa G., Clara N., Antonino G., Nicola T., Silverio T., Giuseppe T., Daniele S., Aandrea M., Lucia M., Aangela V., Emanuela M., Alain G., Valentina M., Enrico C., Loretta D., Alessandra C., Marina C., Luca M., Agnese F., Angelo Fedele S., Domenico C., Luisa C., Emilio B., Nicla L.V., Carlo G., Pia D.S., Rossana M., Enzo V., Ida P., Francesco G., Vito L., Elisa L., Corrado F., Mario R., Vincenzo A., Giuseppina R., Antonio R., Maria Rosaria V., Rossana B., Mirco P., Katia C., Claudio Z., Ornella G., Editta B., Lorenzo L., Icro M., Pietro D.M., Daniele G., Ruggero D.M., Emanuela R., Gennaro C., Alice V., Isabella S., Marco M., Maddalena B., Antonio G., and Patrizia V.
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0301 basic medicine ,Oncology ,Physiology ,Receptor, ErbB-2 ,Clinical Biochemistry ,Ado-Trastuzumab Emtansine ,Settore MED/06 ,body mass index ,HER2-positive metastatic breast cancer ,pertuzumab ,trastuzumab emtansine ,chemistry.chemical_compound ,0302 clinical medicine ,Antineoplastic Agents, Immunological ,Aged, 80 and over ,education.field_of_study ,Univariate analysis ,Middle Aged ,Metastatic breast cancer ,Progression-Free Survival ,Quartile ,030220 oncology & carcinogenesis ,Disease Progression ,Female ,Pertuzumab ,medicine.drug ,Adult ,medicine.medical_specialty ,Population ,Breast Neoplasms ,Antibodies, Monoclonal, Humanized ,03 medical and health sciences ,Breast cancer ,Settore MED/04 - PATOLOGIA GENERALE ,Internal medicine ,medicine ,Humans ,Obesity ,education ,Aged ,business.industry ,nutritional and metabolic diseases ,Cell Biology ,Overweight ,medicine.disease ,030104 developmental biology ,chemistry ,Trastuzumab emtansine ,MED/06 - ONCOLOGIA MEDICA ,business ,Body mass index - Abstract
Body mass index (BMI) is a main indicator of obesity and its association with breast cancer is well established. However, little is known in the metastatic setting, especially in HER2-positive patients. We assessed the influence of BMI on clinical outcomes of patients treated with pertuzumab and/or trastuzumab emtansine (T-DM1) for HER2+ metastatic breast cancer (mBC). BMI was addressed as a categorical variable, being classified on the basis of the following ranges, that is, 18.5-24.9, 25-29.9, and 30.0-34.9, namely, normal weight, overweight, and Class I obesity. The outcomes chosen were progression-free survival to first-line chemotherapy (PFS1) and overall survival (OS). Overall (N = 709), no impact of BMI was observed on PFS1 (p = .15), while BMI ≥ 30 was associated with worse OS (p = .003). In subjects who progressed to first line (N = 575), analyzing data across PFS1 quartiles and strata of disease burden, BMI predicted lower PFS1 in patients within the I PFS1 quartile and with the lowest disease burden (p = .001). Univariate analysis showed a detrimental effect of BMI ≥ 30 on OS for women within the I PFS1 quartile (p = .03). Results were confirmed in multivariate analysis. According to PFS1 quartiles a higher percentage of patients with high BMI and low disease burden progressed within 6 months of therapy. The effect of BMI on prognosis was also confirmed in multivariate analysis of OS for overall population. In our cohort, a BMI ≥ 30 correlated with worse OS in patients with HER2+ mBC who received pertuzumab and/or T-DM1 but had no impact on PFS to first line. BMI predicted worse I PFS1 quartile.
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- 2020
19. Evaluating the role of FAMIly history of cancer and diagnosis of multiple neoplasms in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors. the multicenter FAMI-L1 study
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Fabiana Perrone, Rosa Rita Silva, Cristina Zannori, Paolo Marchetti, Francesco Atzori, Giampiero Porzio, Raffaele Giusti, Domenico Mallardo, Nicola Tinari, Enzo Veltri, Tea Zeppola, Federica De Galitiis, Marcello Tiseo, Alessio Cortellini, Cecilia Anesi, Claudia Mosillo, Alessandro Inno, Marianna Tudini, Stefania Gori, Alain Gelibter, Marco Filetti, Corrado Ficorella, Alessandra Tessitore, Melissa Bersanelli, Andrea Botticelli, Mario Occhipinti, Antonino Grassadonia, Marco Russano, Maria Giuseppa Vitale, Annagrazia Pireddu, Maria Concetta Fargnoli, Francesco Malorgio, Katia Cannita, Federica Pergolesi, Silvia Rinaldi, Michele De Tursi, Maria Rita Migliorino, Francesca Rastelli, Daniela Iacono, Gian Carlo Antonini Cappellini, Rossana Berardi, Pietro Di Marino, Alessandro Parisi, Sergio Bracarda, Paolo A. Ascierto, Daniele Santini, Sebastiano Buti, Federica Zoratto, and Francesco Martella
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0301 basic medicine ,Oncology ,multiple neoplasms ,medicine.medical_specialty ,Multivariate analysis ,medicine.medical_treatment ,Immunology ,Programmed Cell Death 1 Receptor ,ddr genes ,B7-H1 Antigen ,family history of cancer ,immune checkpoint inhibitors ,03 medical and health sciences ,0302 clinical medicine ,Antineoplastic Agents, Immunological ,Internal medicine ,Neoplasms ,medicine ,Immunology and Allergy ,Humans ,cardiovascular diseases ,Family history ,Adverse effect ,RC254-282 ,Retrospective Studies ,Original Research ,business.industry ,Incidence (epidemiology) ,Hazard ratio ,pd-1 ,Cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Retrospective cohort study ,Immunotherapy ,RC581-607 ,medicine.disease ,immunotherapy ,030104 developmental biology ,030220 oncology & carcinogenesis ,Immunologic diseases. Allergy ,business - Abstract
Background: We investigate the role of family history of cancer (FHC) and diagnosis of metachronous and/or synchronous multiple neoplasms (MN), during anti-PD-1/PD-L1 immunotherapy. Design: This was a multicenter retrospective study of advanced cancer patients treated with anti-PD-1/PD-L1 immunotherapy. FHC was collected in lineal and collateral lines, and patients were categorized as follows: FHC-high (in case of cancer diagnoses in both the lineal and collateral family lines), FHC-low (in case of cancer diagnoses in only one family line), and FHC-negative. Patients were also categorized according to the diagnosis of MN as follows: MN-high (>2 malignancies), MN-low (two malignancies), and MN-negative. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and incidence of immune-related adverse events (irAEs) of any grade were evaluated. Results: 822 consecutive patients were evaluated. 458 patients (55.7%) were FHC-negative, 289 (35.2%) were FHC-low, and 75 (9.1%) FHC-high, respectively. 29 (3.5%) had a diagnosis of synchronous MN and 94 (11.4%) of metachronous MN. 108 (13.2%) and 15 (1.8%) patients were MN-low and MN-high, respectively. The median follow-up was 15.6 months. No significant differences were found regarding ORR among subgroups. FHC-high patients had a significantly longer PFS (hazard ratio [HR] = 0.69 [95% CI: 0.48–0.97], p = .0379) and OS (HR = 0.61 [95% CI: 0.39–0.93], p = .0210), when compared to FHC-negative patients. FHC-high was confirmed as an independent predictor for PFS and OS at multivariate analysis. No significant differences were found according to MN categories. FHC-high patients had a significantly higher incidence of irAEs of any grade, compared to FHC-negative patients (p = .0012). Conclusions: FHC-high patients seem to benefit more than FHC-negative patients from anti-PD-1/PD-L1 checkpoint inhibitors.
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- 2020
20. Distinct HR expression patterns significantly affect the clinical behavior of metastatic HER2+ breast cancer and degree of benefit from novel anti-HER2 agents in the real world setting
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Isacco Desideri, G. Tonini, Emanuela Magnolfi, L. Pizzuti, Jennifer Foglietta, Marina Elena Cazzaniga, Adamo, Patrizia Vici, Enrico Cortesi, Emanuela Risi, G. D'Auria, Loretta D'Onofrio, Mario Roselli, Isabella Sperduti, N. Tinari, Nicola D’Ostilio, A. Vaccaro, Icro Meattini, Federica Tomao, Giacomo Barchiesi, B Di Cocco, F Cardillo, Enzo Veltri, Claudia Omarini, Mirco Pistelli, Clara Natoli, Carlo Garufi, E. Landucci, M. Mauri, Rosanna Mirabelli, Federico Piacentini, Domenico Corsi, A.F. Scinto, Alice Villa, Alain Gelibter, C. De Angelis, Marco Mazzotta, Gennaro Ciliberto, Claudio Zamagni, Giuseppe Sanguineti, Fiorentino Izzo, Elizabeth H. Baldini, Rossana Berardi, Grr Ricciardi, Maddalena Barba, Ornella Garrone, Ida Paris, Luisa Carbognin, A. Botticelli, Giuseppina Sarobba, Silverio Tomao, Antonio Astone, Lucia Mentuccia, P Del Medico, Lorusso, Daniele Santini, M. Della Giulia, Riccardo Samaritani, Francesco Giotta, Alessandra Cassano, Laura Iezzi, Maria Agnese Fabbri, R De Maria, Eriseld Krasniqi, Raffaele Giusti, Sini, Lorenzo Livi, Ernesto Rossi, Andrea Michelotti, Emilio Bria, A Di Leo, Luca Moscetti, Corrado Ficorella, Antonino Grassadonia, Roberta Sarmiento, Katia Cannita, Filippo Greco, Sandro Barni, Elena Fiorio, Teresa Gamucci, Magri, Antonio Russo, M. De Tursi, N. La Verde, Daniele Generali, Paolo Marchetti, Pizzuti, L, Krasniqi, E, Barchiesi, G, Della Giulia, M, Izzo, F, Sanguineti, G, Marchetti, P, Mazzotta, M, Giusti, R, Botticelli, A, Gamucci, T, Natoli, C, Grassadonia, A, Tinari, N, Iezzi, L, Tomao, S, Tomao, F, Tonini, G, Santini, D, Astone, A, Michelotti, A, De Angelis, C, Mentuccia, L, Vaccaro, A, Magnolfi, E, Gelibter, A, Magri, V, Cortesi, E, D'Onofrio, L, Cassano, A, Rossi, E, Cazzaniga, M, Moscetti, L, Omarini, C, Piacentini, F, Fabbri, M, Scinto, A, Corsi, D, Carbognin, L, Bria, E, La Verde, N, Samaritani, R, Garufi, C, Barni, S, Mirabelli, R, Sarmiento, R, Veltri, E, D'Auria, G, Paris, I, Giotta, F, Lorusso, V, Cardillo, F, Landucci, E, Mauri, M, Ficorella, C, Roselli, M, Adamo, V, Ricciardi, G, Russo, A, Berardi, R, Pistelli, M, Fiorio, E, Cannita, K, Sini, V, D'Ostilio, N, Foglietta, J, Greco, F, Zamagni, C, Garrone, O, Di Cocco, B, Baldini, E, Livi, L, Desideri, I, Meattini, I, Sarobba, G, Del Medico, P, De Tursi, M, Generali, D, De Maria, R, Risi, E, Ciliberto, G, Sperduti, I, Villa, A, Barba, M, Di Leo, A, and Vici, P
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Oncology ,Cancer Research ,Multivariate analysis ,Settore MED/06 - Oncologia Medica ,Receptor, ErbB-2 ,T-DM1 ,Estrogen receptor ,0302 clinical medicine ,ErbB-2 ,Trastuzumab ,Receptors ,Antineoplastic Combined Chemotherapy Protocols ,80 and over ,Molecular Targeted Therapy ,Neoplasm Metastasis ,Cancer Therapy and Prevention ,Progesterone ,Aged, 80 and over ,advanced breast cancer ,Tumor ,real world ,Middle Aged ,Prognosis ,Metastatic breast cancer ,Immunohistochemistry ,Gene Expression Regulation, Neoplastic ,trastuzumab ,Receptors, Estrogen ,030220 oncology & carcinogenesis ,Female ,HER2 positive ,pertuzumab ,Adult ,Aged ,Biomarkers, Tumor ,Breast Neoplasms ,Humans ,Neoplasm Staging ,Receptors, Progesterone ,Pertuzumab ,medicine.drug ,Receptor ,medicine.medical_specialty ,T‐DM1 ,chemotherapy ,03 medical and health sciences ,Breast cancer ,Settore MED/04 - PATOLOGIA GENERALE ,Internal medicine ,medicine ,Neoplastic ,business.industry ,medicine.disease ,Estrogen ,Settore CHIM/08 - Chimica Farmaceutica ,Gene Expression Regulation ,MED/06 - ONCOLOGIA MEDICA ,business ,Biomarkers ,Hormone - Abstract
We analyzed data from 738 HER2‐positive metastatic breast cancer (mbc) patients treated with pertuzumab‐based regimens and/or T‐DM1 at 45 Italian centers. Outcomes were explored in relation to tumor subtype assessed by immunohistochemistry (IHC). The median progression‐free survival at first‐line (mPFS1) was 12 months. Pertuzumab as first‐line conferred longer mPFS1 compared to other first‐line treatments (16 vs. 9 months, p = 0.0001), regardless of IHC subtype. Median PFS in second‐line (mPFS2) was 7 months, with no difference by IHC subtype, but it was more favorable with T‐DM1 compared to other agents (7 vs. 6 months, p = 0.03). There was no PFS2 gain in patients with tumors expressing both hormonal receptors (HRs; p = 0.17), while a trend emerged for tumors with one HR (p = 0.05). Conversely, PFS2 gain was significant in HRs‐negative tumors (p = 0.04). Median overall survival (mOS) was 74 months, with no significant differences by IHC subtypes. Survival rates at 2 and 3 years in patients treated with T‐DM1 in second‐line after pertuzumab were significantly lower compared to pertuzumab‐naïve patients (p = 0.01). When analyzed by IHC subtype, the outcome was confirmed if both HRs or no HRs were expressed (p = 0.02 and p = 0.006, respectively). Our results confirm that HRs expression impacts the clinical behavior and novel treatment‐related outcomes of HER2‐positive tumors when treatment sequences are considered. Moreover, multivariate analysis showed that HRs expression had no effect on PFS and OS. Further studies are warranted to confirm our findings and clarify the interplay between HER2 and estrogen receptor pathways in HER2‐positive (mbc) patients., What's new? About half of breast cancers positive for human epidermal growth factor (HER2) also express hormone receptors but the impact of hormone receptor status on the success of HER2‐directed treatments is not fully explored. Here the authors retrospectively assessed tumor behavior and treatment outcomes in 738 women with HER2+ metastatic breast cancer treated with new generation anti‐HER2 agents. Distinct hormone receptor expression patterns significantly affected the progression free and overall survival, justifying further studies to define optimal treatment regimens and the interplay between hormone receptor and HER2 signaling.
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- 2020
21. Analysis of systemic inflammatory biomarkers in neuroendocrine carcinomas of the lung: prognostic and predictive significance of NLR, LDH, ALI, and LIPI score
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Marta Peri, Sergio Rizzo, Luciana Irtelli, Antonio Russo, Viviana Bazan, Antonino Grassadonia, Valerio Gristina, Michele De Tursi, Marta Castiglia, Nadia Barraco, Antonio Galvano, A. Guarini, Clara Natoli, Alessandro Bertani, Galvano A., Peri M., Guarini A.A., Castiglia M., Grassadonia A., De Tursi M., Irtelli L., Rizzo S., Bertani A., Gristina V., Barraco N., Russo A., Natoli C., and Bazan V.
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Oncology ,medicine.medical_specialty ,Lung ,Blood based biomarkers ,business.industry ,Settore MED/06 - Oncologia Medica ,small-cell lung cancer (SCLC) ,systemic inflammatory response ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Inflammatory biomarkers ,lcsh:RC254-282 ,Neuroendocrine Carcinomas ,medicine.anatomical_structure ,Internal medicine ,medicine ,Prognostic biomarker ,Neuroendocrine carcinoma ,Original Article ,business ,predictive biomarker ,prognostic biomarker ,neuroendocrine tumor ,Predictive biomarker ,blood-based biomarker - Abstract
Background: Lung neuroendocrine carcinoma (NEC) is characterized by aggressive clinical behavior and lack of treatment advances. We evaluate the prognostic and the predictive roles of systemic inflammatory biomarkers in patient circulating blood: neutrophil–lymphocyte ratio (NLR), lactate dehydrogenase (LDH), advanced lung cancer inflammation index (ALI), and the Lung Immune Prognostic Index (LIPI) score. Methods: A total of 120 patients with small-cell lung cancer (SCLC) ( n = 110) and large cell neuroendocrine carcinoma (LCNEC) ( n = 10) were enrolled. Overall survival (OS) was evaluated by Kaplan–Meier estimator and univariate and multivariate Cox proportional hazard analyses were performed to determine prognostic factors associated with OS while χ2 test was used for categorical data. Results: NLR cutoff value was 1.93. NLR was measured before and after first-line chemotherapy; 25 (21%) patients had higher NLR (delta NLR >1), whereas NLR was lower in 37 (31%). At the univariate analysis, median OS was 12 months: OS for SCLC and LCNEC were 11 months and 14 months, respectively. OS had a prognostic positive value in patients with pre-treatment NLR 1.93) had an increased probability of tumor progression ( p = 0.045, χ2 test). Conclusion: This study demonstrated that systemic inflammatory biomarkers could facilitate the understanding of survival differences in the clinical management of lung NEC patients, underlying the need for prospective biomarker-driven studies in the immune checkpoint inhibitors setting.
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- 2020
22. The Benzimidazole-Based Anthelmintic Parbendazole: A Repurposed Drug Candidate That Synergizes with Gemcitabine in Pancreatic Cancer
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Nicola Tinari, Viviana di Giacomo, Roberto Cirilli, Antonino Grassadonia, Laura De Lellis, Serena Veschi, Rosalba Florio, Adriano Casulli, Fabio Verginelli, Simone Carradori, Amelia Cataldi, Sara Pagotto, Rosa Amoroso, and Alessandro Cama
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0301 basic medicine ,Cancer Research ,pancreatic ductal adenocarcinoma ,Article ,03 medical and health sciences ,combined treatments ,0302 clinical medicine ,Pancreatic cancer ,synergism ,medicine ,Viability assay ,Mitosis ,IC50 ,Mitotic catastrophe ,mitotic catastrophe ,benzimidazoles ,drug repurposing ,Chemistry ,medicine.disease ,Gemcitabine ,Drug repositioning ,030104 developmental biology ,Oncology ,Apoptosis ,030220 oncology & carcinogenesis ,Cancer research ,medicine.drug - Abstract
Pancreatic cancer (PC) is one of the most lethal, chemoresistant malignancies and it is of paramount importance to find more effective therapeutic agents. Repurposing of non-anticancer drugs may expand the repertoire of effective molecules. Studies on repurposing of benzimidazole-based anthelmintics in PC and on their interaction with agents approved for PC therapy are lacking. We analyzed the effects of four Food and Drug Administration (FDA)-approved benzimidazoles on AsPC-1 and Capan-2 pancreatic cancer cell line viability. Notably, parbendazole was the most potent benzimidazole affecting PC cell viability, with half maximal inhibitory concentration (IC50) values in the nanomolar range. The drug markedly inhibited proliferation, clonogenicity and migration of PC cell lines through mechanisms involving alteration of microtubule organization and formation of irregular mitotic spindles. Moreover, parbendazole interfered with cell cycle progression promoting G2/M arrest, followed by the emergence of enlarged, polyploid cells. These abnormalities, suggesting a mitotic catastrophe, culminated in PC cell apoptosis, are also associated with DNA damage in PC cell lines. Remarkably, combinations of parbendazole with gemcitabine, a drug employed as first-line treatment in PC, synergistically decreased PC cell viability. In conclusion, this is the first study providing evidence that parbendazole as a single agent, or in combination with gemcitabine, is a repurposing candidate in the currently dismal PC therapy.
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- 2019
23. Circulating Cancer Stem Cell-Derived Extracellular Vesicles as a Novel Biomarker for Clinical Outcome Evaluation
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Laura Pierdomenico, Clara Natoli, Sebastiano Miscia, Nicola Tinari, Damiana Pieragostino, Paola Lanuti, Fausta Ciccocioppo, Davide Brocco, I. G. Rapposelli, Vincenzo Graziano, P. Del Boccio, Maria Concetta Cufaro, Eva Ercolino, Marta Peri, Giuseppina Bologna, Paola Simeone, Marco Marchisio, Antonino Grassadonia, M. De Tursi, P. Di Marino, Grassadonia, A [0000-0002-2459-0661], Del Boccio, P [0000-0003-1653-2194], Marchisio, M [0000-0003-3058-3422], Natoli, C [0000-0001-7295-0230], and Apollo - University of Cambridge Repository
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Oncology ,CD31 ,medicine.medical_specialty ,Article Subject ,32 Biomedical and Clinical Sciences ,Proteomics ,lcsh:RC254-282 ,Flow cytometry ,Clinical Research ,Cancer stem cell ,Internal medicine ,medicine ,2.1 Biological and endogenous factors ,Cancer ,2 Aetiology ,medicine.diagnostic_test ,business.industry ,Prevention ,Cell sorting ,3211 Oncology and Carcinogenesis ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Precision medicine ,medicine.disease ,4.1 Discovery and preclinical testing of markers and technologies ,Biomarker (medicine) ,4 Detection, screening and diagnosis ,business ,Research Article ,4.2 Evaluation of markers and technologies - Abstract
The recent introduction of the “precision medicine” concept in oncology pushed cancer research to focus on dynamic measurable biomarkers able to predict responses to novel anticancer therapies in order to improve clinical outcomes. Recently, the involvement of extracellular vesicles (EVs) in cancer pathophysiology has been described, and given their release from all cell types under specific stimuli, EVs have also been proposed as potential biomarkers in cancer. Among the techniques used to study EVs, flow cytometry has a high clinical potential. Here, we have applied a recently developed and simplified flow cytometry method for circulating EV enumeration, subtyping, and isolation from a large cohort of metastatic and locally advanced nonhaematological cancer patients (N = 106); samples from gender- and age-matched healthy volunteers were also analysed. A large spectrum of cancer-related markers was used to analyse differences in terms of peripheral blood circulating EV phenotypes between patients and healthy volunteers, as well as their correlation to clinical outcomes. Finally, EVs from patients and controls were isolated by fluorescence-activated cell sorting, and their protein cargoes were analysed by proteomics. Results demonstrated that EV counts were significantly higher in cancer patients than in healthy volunteers, as previously reported. More interestingly, results also demonstrated that cancer patients presented higher concentrations of circulating CD31+ endothelial-derived and tumour cancer stem cell-derived CD133 + CD326- EVs, when compared to healthy volunteers. Furthermore, higher levels of CD133 + CD326− EVs showed a significant correlation with a poor overall survival. Additionally, proteomics analysis of EV cargoes demonstrated disparities in terms of protein content and function between circulating EVs in cancer patients and healthy controls. Overall, our data strongly suggest that blood circulating cancer stem cell-derived EVs may have a role as a diagnostic and prognostic biomarker in cancer.
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- 2019
24. 68P High blood concentration of circulating cancer stem cell-derived extracellular vesicles is associated with poor survival in advanced colorectal cancer patients
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Davide Brocco, P. Di Sebastiano, Alessandro Cama, Antonino Grassadonia, P. Di Marino, Marco Marchisio, Paola Lanuti, Giuseppina Bologna, Paola Simeone, L. De Lellis, Nicola Tinari, Sebastiano Miscia, M. De Tursi, and Serena Veschi
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Advanced colorectal cancer ,Oncology ,Blood concentration ,Cancer stem cell ,business.industry ,Cancer research ,Medicine ,Hematology ,business ,Extracellular vesicles - Published
- 2021
25. Neoadjuvant chemotherapy in triple-negative breast cancer: A multicentric retrospective observational study in real-life setting
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Patrizia Vici, Nicola Tinari, Alessandra Cassano, Giuseppe Sanguineti, Luigi Di Lauro, Michele De Tursi, Antonio Astone, A. Vaccaro, Maddalena Barba, Andrea Michelotti, Laura Iezzi, Luisa Carbognin, Gennaro Ciliberto, Laura Pizzuti, Antonino Grassadonia, Antonio Giordano, Paolo Marchetti, Paola Fuso, Francesca Conti, E. Landucci, Clara Natoli, Marcello Maugeri-Saccà, Teresa Gamucci, Gianni Iafrate, Lucia Mentuccia, Domenico Sergi, Luca Moscetti, Isabella Sperduti, Emanuela Magnolfi, and Andrea Botticelli
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0301 basic medicine ,Oncology ,Time Factors ,Multivariate analysis ,Physiology ,medicine.medical_treatment ,Clinical Biochemistry ,Triple Negative Breast Neoplasms ,Kaplan-Meier Estimate ,0302 clinical medicine ,Risk Factors ,Antineoplastic Combined Chemotherapy Protocols ,Odds Ratio ,Anthracyclines ,Adjuvant ,Neoadjuvant therapy ,Triple-negative breast cancer ,Univariate analysis ,Middle Aged ,Neoadjuvant Therapy ,Treatment Outcome ,Italy ,Chemotherapy, Adjuvant ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,rKi-67 ,Disease Progression ,triple-negative breast cancer ,Female ,Taxoids ,long-term outcomes ,neoadjuvant chemotherapy ,Adult ,medicine.medical_specialty ,pathological complete response ,Aged ,Chi-Square Distribution ,Disease-Free Survival ,Humans ,Ki-67 Antigen ,Multivariate Analysis ,Neoplasm Grading ,Proportional Hazards Models ,Retrospective Studies ,Cell Biology ,03 medical and health sciences ,Breast cancer ,Internal medicine ,medicine ,Chemotherapy ,Settore MED/06 - ONCOLOGIA MEDICA ,Proportional hazards model ,business.industry ,Retrospective cohort study ,medicine.disease ,030104 developmental biology ,Concomitant ,business - Abstract
We aimed to assess the efficacy of neoadjuvant chemotherapy (NACT) in a cohort of 213 triple-negative breast cancer (TNBC) patients treated in real-world practice at eight Italian cancer centers. We computed descriptive statistics for all the variable of interest. Factors testing significant in univariate analysis were included in multivariate models. Survival data were compared by Kaplan-Meier curves and log-rank test. The median follow-up was 45 months. We observed 60 (28.2%) pathological complete response (pCR). The sequential anthracyclines-taxanes-based regimens produced the highest rate of pCR (42.6%), followed by concomitant anthracycline-taxane (24.2%), and other regimens (15.6%) (p = 0.008). When analyzing the role of baseline Ki-67, a 50% cut-off was the optimal threshold value for pCR prediction (p = 0.0005). The 5-year disease-free survival (DFS) was 57.3% and the 5-year overall survival (OS) was 70.8%. In patients not achieving pCR, the optimal Ki-67 variation between biopsy and surgical specimen with prognostic relevance on long-term outcomes was 13% (p = 0.04). Patients with a Ki-67 reduction (rKi-67)13% had worse outcomes compared to those who experienced pCR or a rKi-67≥13%. The number of NACT cycles also affected long-term outcomes (5-year DFS 65.7% vs 51.6% in patients having received6 cycles compared with their counterparts, p = 0.02). In multivariate analysis, node status, grading, and bio-pathological treatment response (including pCR and rKi-67) impacted DFS and OS. Our results confirmed the advantage conferred by more than 6 cycles of a sequential antracycline-taxane-based NACT. Higher baseline Ki-67 values shows greater predictive significance on pathogical response, while the rKi-67 plays a prognostic role on long-term outcomes.
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- 2017
26. Long-term outcome of breast cancer patients with pathologic N3a lymph node stage
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Jamara Giampietro, Marinella Zilli, Teresa Gamucci, Laura Iezzi, Antonino Grassadonia, Maria Teresa Scognamiglio, Vincenzo Graziano, Clara Natoli, Nicola Tinari, Laura Pizzuti, Patrizia Vici, Lucia Mentuccia, and Luca Moscetti
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Axillary lymph nodes ,business.industry ,Lymphovascular invasion ,Proportional hazards model ,Hazard ratio ,General Medicine ,medicine.disease ,Surgery ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Breast cancer ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Stage (cooking) ,business ,Survival rate ,Lymph node - Abstract
Purpose To evaluate factors influencing the long-term outcome of patients presenting with 10 or more metastatic axillary lymph nodes (pN3a) after surgery for primary breast cancer. Method Between January 1990 and December 2015, a total of 130 patients with pN3a breast cancer at surgery were identified in our Institutions and included in the study. Twenty-nine of them (22.3%) received neoadjuvant chemotherapy. The Multivariate Cox proportional hazards model was used to determine independent prognostic factors associated with DFS and OS. Results After a median follow-up of 6.4 years (range 0.87–25 years), 2 patients had a local relapse, 59 distant metastases (1 with local relapse) and 52 patients died. The 5-year DFS and OS rates were 61.8% and 71.5%, respectively. At multivariate analysis, pN3a stage after neoadjuvant chemotherapy (ypN3a) was significantly associated with increased risk of recurrence (HR 1.92, p = 0.02) and death (HR 2.05, p = 0.029). Absence of progesterone receptor (PR) expression was the most important tumor characteristic associated with poor prognosis, both in terms of recurrence (HR 2.55, p Conclusions The results of this study indicate that ypN3a stage, lack of expression of PR, and Ki-67 ≥ 20% negatively affect long-term outcome of patients with pN3a breast cancer.
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- 2017
27. A Real-World Multicentre Retrospective Study of Paclitaxel-Bevacizumab and Maintenance Therapy as First-Line for HER2-Negative Metastatic Breast Cancer
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Andrea Michelotti, M.G. Sarobba, Antonino Astone, Teresa Gamucci, Lucia Mentuccia, Laura Pizzuti, Paolo Marchetti, Alessandra Cassano, Emanuela Magnolfi, Antonio Giordano, Luigi Di Lauro, Isabella Sperduti, Cecilia Nisticò, Patrizia Vici, Domenico Sergi, Marcello Maugeri-Saccà, Maddalena Barba, Simonetta Buglioni, Luca Moscetti, F. Angelini, Claudia De Angelis, Arianna Pellegrino, Ernesto Rossi, Valentina Sini, I. Bertolini, Domenica Pellegrini, Clara Natoli, Michela Palleschi, Antonino Grassadonia, A. Vaccaro, and Alessandra Fabi
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Bevacizumab ,Physiology ,Clinical Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Maintenance therapy ,Internal medicine ,medicine ,Proportional hazards model ,business.industry ,Cancer ,Retrospective cohort study ,Cell Biology ,medicine.disease ,Metastatic breast cancer ,Discontinuation ,030104 developmental biology ,Paclitaxel ,chemistry ,030220 oncology & carcinogenesis ,business ,medicine.drug - Abstract
Bevacizumab in combination with taxanes in HER2-negative metastatic breast cancer (MBC) patients has shown improved progression-free survival (PFS), despite the lack of clear overall survival (OS) benefit. We performed a retrospective analysis to evaluate the impact of paclitaxel-bevacizumab and of maintenance therapy with bevacizumab (BM) and endocrine therapy (ET) in the real-world practice. We identified 314 HER2-negative MBC patients treated in 12 cancer centers. Overall, the median PFS and OS were 14 and 40 months, respectively. Among the 254 patients potentially eligible for BM, 183 received BM after paclitaxel discontinuation until progression/toxicity. PFS and OS were improved in patients who had received BM in comparison with those potentially eligible but who did not receive BM (P
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- 2016
28. Prognostic relevance of DNA damage and repair biomarkers in elderly patients with hormone-receptor-positive breast cancer treated with neoadjuvant hormone therapy: evidence from the real-world setting
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Laura Pizzuti, Cristiana Ercolani, Marcello Maugeri-Saccà, Irene Terrenato, Luciano Mariani, Marco Mazzotta, Francesca Sperati, Enrico Vizza, Antonino Grassadonia, Maddalena Barba, Camilla Marinelli, Silverio Tomao, Patrizia Vici, Nicola Tinari, Domenico Angelucci, Domenico Sergi, Anna Di Benedetto, Gennaro Ciliberto, Laura Iezzi, Clara Natoli, and G. Paoletti
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,DNA damage ,medicine.medical_treatment ,hormone-receptor-positive breast cancer ,elderly patients ,lcsh:RC254-282 ,prognostic biomarkers ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Internal medicine ,medicine ,Original Research ,business.industry ,DNA damage and repair ,Endocrine therapy ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,030104 developmental biology ,Hormone receptor ,030220 oncology & carcinogenesis ,Hormone therapy ,business ,neoadjuvant hormone therapy - Abstract
Background: The logic behind the outcome of endocrine therapy in breast cancer has long remained poorly understood. The prognostic role of DNA damage and repair biomarkers (DDR) was explored in postmenopausal, hormone-receptor-positive breast cancer patients treated with neoadjuvant hormone therapy (NAHT). Methods: Data on 55 patients were included. The phosphorylated ataxia-teleangectasia and Rad3-related protein (pATR), phosphorylated ataxia-telangiectasia mutated (ATM) kinase, and phosphorylated H2A Histone Family Member X (γ-H2AX) were evaluated by immunohistochemistry in paired tissues collected at baseline and following NAHT. Biomarkers were considered both singularly and within signatures. Ki-67 percentage change was the primary biomarker endpoint. Classical endpoints were also considered. Results: The most favorable Ki-67 outcome was associated with the γ-H2AX/pATM signature ( p = 0.011). In models of Ki-67 reduction, ‘luminal B’ subtype, higher grade of anaplasia, and the γ-H2AX/pATM signature tested as significant ( p < 0.05 for all). Results were confirmed in multivariate analysis. No association was observed with pathologic response. An increase of ∆γ-H2AX in paired breast tissues was associated with longer event-free survival ( p = 0.027) and overall survival ( p = 0.042). In Cox models, both survival outcomes were solely affected by grade of anaplasia, with less favorable prognosis in the highest grades ( p < 0.05 for both). Conclusions: We report novel evidence of the prognostic role of DDR biomarkers on important patient outcomes in postmenopausal hormone-receptor-positive breast cancer patients treated with NAHT. If confirmed in future and adequately sized trials, our results may help inform therapeutic decisions and clarify underlying biological mechanisms.
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- 2019
29. Palbociclib plus endocrine therapy in HER2 negative, hormonal receptor-positive, advanced breast cancer: A real-world experience
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Michele De Tursi, Marco Mazzotta, Armando Orlandi, Marina Elena Cazzaniga, Enrico Cortesi, Maddalena Barba, Laura Iezzi, Giuseppe Tonini, E. Landucci, Lucio Laudadio, Domenico Sergi, Alessandra Cassano, Giuseppe Sanguineti, Nicla La Verde, Riccardo Samaritani, Patrizia Seminara, Antonio Russo, Claudio Zamagni, Simone Scagnoli, Valentina Magri, Ramy Kayal, Enzo Veltri, Francesca Aroldi, Clara Natoli, Ilaria Portarena, Samantha Forciniti, Laura Ferrari, Lucia Mentuccia, Gennaro Ciliberto, Daniele Santini, Teresa Gamucci, Filippo Greco, Silvia Carpano, Mario Roselli, Sandro Barni, A. Fabbri, Isabella Sperduti, A. Vaccaro, Ida Paris, Daniela Rubino, Ruggero De Maria, Patrizia Vici, Claudia De Angelis, Giulia Pomati, Luisa Carbognin, Simona Vallarelli, Antonino Grassadonia, Mirco Pistelli, A.F. Scinto, Katia Cannita, Andrea Michelotti, Domenico Corsi, E. Capomolla, Corrado Ficorella, Nicola Tinari, Vito Lorusso, Rossana Berardi, Andrea Botticelli, Antonio Giordano, Silverio Tomao, Laura Pizzuti, Paolo Marchetti, Maria Giuseppina Sarobba, Valentina Sini, Luca Moscetti, Lucrezia Diodati, Maria Vincenza Mancini, Luciano Mariani, Pizzuti, L, Giordano, A, Michelotti, A, Mazzotta, M, Natoli, C, Gamucci, T, De Angelis, C, Landucci, E, Diodati, L, Iezzi, L, Mentuccia, L, Fabbri, A, Barba, M, Sanguineti, G, Marchetti, P, Tomao, S, Mariani, L, Paris, I, Lorusso, V, Vallarelli, S, Cassano, A, Airoldi, F, Orlandi, A, Moscetti, L, Sergi, D, Sarobba, M, Tonini, G, Santini, D, Sini, V, Veltri, E, Vaccaro, A, Ferrari, L, De Tursi, M, Tinari, N, Grassadonia, A, Greco, F, Botticelli, A, La Verde, N, Zamagni, C, Rubino, D, Cortesi, E, Magri, V, Pomati, G, Scagnoli, S, Capomolla, E, Kayal, R, Scinto, A, Corsi, D, Cazzaniga, M, Laudadio, L, Forciniti, S, Mancini, M, Carbognin, L, Seminara, P, Barni, S, Samaritani, R, Roselli, M, Portarena, I, Russo, A, Ficorella, C, Cannita, K, Carpano, S, Pistelli, M, Berardi, R, De Maria, R, Sperduti, I, Ciliberto, G, Vici, P, Pizzuti, Laura, Giordano, Antonio, Michelotti, Andrea, Mazzotta, Marco, Natoli, Clara, Gamucci, Teresa, De Angelis, Claudia, Landucci, Elisabetta, Diodati, Lucrezia, Iezzi, Laura, Mentuccia, Lucia, Fabbri, Agnese, Barba, Maddalena, Sanguineti, Giuseppe, Marchetti, Paolo, Tomao, Silverio, Mariani, Luciano, Paris, Ida, Lorusso, Vito, Vallarelli, Simona, Cassano, Alessandra, Airoldi, Francesca, Orlandi, Armando, Moscetti, Luca, Sergi, Domenico, Sarobba, Maria Giuseppina, Tonini, Giuseppe, Santini, Daniele, Sini, Valentina, Veltri, Enzo, Vaccaro, Angela, Ferrari, Laura, De Tursi, Michele, Tinari, Nicola, Grassadonia, Antonino, Greco, Filippo, Botticelli, Andrea, La Verde, Nicla, Zamagni, Claudio, Rubino, Daniela, Cortesi, Enrico, Magri, Valentina, Pomati, Giulia, Scagnoli, Simone, Capomolla, Elisabetta, Kayal, Ramy, Scinto, Angelo Fedele, Corsi, Domenico, Cazzaniga, Marina, Laudadio, Lucio, Forciniti, Samantha, Mancini, Maria, Carbognin, Luisa, Seminara, Patrizia, Barni, Sandro, Samaritani, Riccardo, Roselli, Mario, Portarena, Ilaria, Russo, Antonio, Ficorella, Corrado, Cannita, Katia, Carpano, Silvia, Pistelli, Mirco, Berardi, Rossana, De Maria, Ruggero, Sperduti, Isabella, Ciliberto, Gennaro, and Vici, Patrizia
- Subjects
Male ,0301 basic medicine ,Oncology ,Pyridines ,Receptor, ErbB-2 ,Physiology ,Clinical Biochemistry ,Piperazines ,chemistry.chemical_compound ,0302 clinical medicine ,Exemestane ,Antineoplastic Combined Chemotherapy Protocols ,advanced breast cancer ,hormonal therapy ,endocrine resistance ,palbociclib ,real-world setting ,Breast ,Aged, 80 and over ,advanced breast cancer, hormonal therapy ,Middle Aged ,Treatment Outcome ,Receptors, Estrogen ,030220 oncology & carcinogenesis ,Toxicity ,Female ,Receptors, Progesterone ,medicine.drug ,Adult ,Cell Biology ,medicine.medical_specialty ,Breast Neoplasms ,Palbociclib ,Neutropenia ,Disease-Free Survival ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Aged ,Everolimus ,Settore MED/06 - ONCOLOGIA MEDICA ,business.industry ,Cancer ,medicine.disease ,Confidence interval ,030104 developmental biology ,chemistry ,MED/06 - ONCOLOGIA MEDICA ,business ,Hormone - Abstract
Data from 423 human epidermal growth factor receptor 2-negative (HER2−), hormone receptor-positive (HR+) advanced breast cancer (aBC) patients treated with palbociclib and endocrine therapy (ET) were provided by 35 Italian cancer centers and analyzed for treatment outcomes. Overall, 158 patients were treated in first line and 265 in second/later lines. We observed 19 complete responses and 112 partial responses. The overall response rate (ORR) was 31% (95% confidence interval [CI], 26.6–35.4) and clinical benefit was 52.7% (95% CI, 48–57.5). ORR was negatively affected by prior exposure to everolimus/exemestane (p = 0.002) and favorably influenced by early line-treatment (p < 0.0001). At 6 months, median progression-free survival was 12 months (95% CI, 8–16) and median overall survival was 24 months (95% CI, 17–30). More favorable outcomes were associated with palbociclib in early lines, no visceral metastases and no prior everolimus/exemestane. The main toxicity reported was neutropenia. Our results provide further support to the use of palbociclib with ET in HER2−, HR+ aBC. Differences in outcomes across patients subsets remain largely unexplained.
- Published
- 2019
30. Palliative radiotherapy in advanced cancer patients treated with immune‑checkpoint inhibitors: The PRACTICE study
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Nunziata D'Abbiero, Giampiero Porzio, Sebastiano Buti, Maria Michiara, Paola Bordi, Fabiana Perrone, Pietro Di Marino, Gianluca Gravina, Melissa Bersanelli, Alessandro Leonetti, Nicola Tinari, Domenico Genovesi, Elisa Giaiacopi, Michele De Tursi, Luciana Caravatta, Elisabetta Lattanzi, Marianna Trignani, Corrado Ficorella, Alessio Cortellini, Salvatore Trapani, Maria Giulia Canè, Marcello Tiseo, Antonino Grassadonia, Katia Cannita, and Clara Natoli
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,anti-PD-L1 ,abscopal effect ,medicine.medical_treatment ,General Biochemistry, Genetics and Molecular Biology ,immune checkpoint inhibitors ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Progression-free survival ,General Pharmacology, Toxicology and Pharmaceutics ,Adverse effect ,immunosuppression ,business.industry ,General Neuroscience ,Abscopal effect ,Cancer ,food and beverages ,Immunosuppression ,General Medicine ,Immunotherapy ,Articles ,medicine.disease ,Immune checkpoint ,Blockade ,030104 developmental biology ,030220 oncology & carcinogenesis ,anti-PD-1 ,palliative radiotherapy ,immunotherapy ,business - Abstract
In the present study, the influence of purely palliative radiotherapy (pRT) on the outcomes of patients with advanced cancer undergoing immune checkpoint blockade was evaluated. Patients were stratified into three groups: Patients who had received pRT within 6 months prior to the initiation of immunotherapy (previous pRT); patients who received pRT during immunotherapy (concurrent pRT); and patients who did not receive RT prior to or during immunotherapy (no RT group), and these groups were compared. The median overall survival (mOS), median progression free survival (mPFS) and median time-to-treatment failure (mTTF) for the previous pRT group were significantly shorter compared with the no RT group (mOS, 3.6 vs. 12.1 months, respectively, P=0.0095; mPFS 1.8 vs. 5.4 months, respectively, P=0.0016; mTTF 1.8 vs. 5.7 months, respectively, P=0.0035). The concurrent pRT group had a longer mTTF compared with the previous pRT group and similar outcomes to the no RT group. In the previous pRT group, 26.9% of the patients experienced immune-related adverse events compared with 40.1% of patients in the no RT group. Despite the use of pRT during immunotherapy being considered safe, the results of the present study suggest that pRT has a negative effect on immune balance.
- Published
- 2019
31. Correlations Between the Immune-related Adverse Events Spectrum and Efficacy of Anti-PD1 Immunotherapy in NSCLC Patients
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Rosa Rita Silva, Antonino Grassadonia, Marco Russano, Michele De Tursi, Biagio Ricciuti, Raffaele Giusti, Rita Chiari, Katia Cannita, Sebastiano Buti, Daniele Santini, Corrado Ficorella, Federica Zoratto, Paolo Marchetti, Melissa Bersanelli, Maria Rita Migliorino, Paola Bordi, Giampiero Porzio, N. Tinari, Fabiana Perrone, Francesco Atzori, Enzo Veltri, Pietro Di Marino, Cecilia Anesi, Marco Filetti, Tea Zeppola, Rossana Berardi, Alessio Cortellini, Giulio Metro, Marcello Tiseo, Silvia Rinaldi, Marianna Tudini, Francesco Malorgio, Daniela Iacono, Annagrazia Pireddu, and Carlo Garufi
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,Multivariate analysis ,medicine.medical_treatment ,Pembrolizumab ,carcinoma ,NSCLC ,survival analysis ,0302 clinical medicine ,Immune-related adverse events ,Carcinoma, Non-Small-Cell Lung ,italy ,middle aged ,80 and over ,antibodies ,humans ,Aged, 80 and over ,humanized ,adult ,aged ,retrospective studies ,female ,Nivolumab ,030220 oncology & carcinogenesis ,young adult ,Immunotherapy ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,immune system diseases ,monoclonal ,lung neoplasms ,Antibodies, Monoclonal, Humanized ,programmed cell death 1 receptor ,03 medical and health sciences ,Immune system ,male ,Internal medicine ,medicine ,Adverse effect ,Lung cancer ,business.industry ,Surrogate endpoint ,medicine.disease ,non-small-cell lung ,030104 developmental biology ,drug-related side effects and adverse reactions ,treatment outcome ,immune-related adverse events ,immunotherapy ,nivolumab ,nsclc ,pembrolizumab ,business - Abstract
Immune-related adverse events (irAEs) developed during immunotherapy with anti-PD-1 agents, could be a predictive surrogate marker of clinical benefit in patients with advanced non-small-cell lung cancer (NSCLC).Patients with NSCLC, treated with anti-PD-1 agents, were retrospectively evaluated. Univariate and multivariate analyses were performed to evaluate the relationships between types of irAEs (differentiated according to system/organ involved and to single-site/multiple-site), overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). We further performed a 6-week landmark analysis.A total of 559 patients were enrolled; 231 patients (41.3%) developed irAEs of any grade and 50 patients (8.9%) G3/G4 events; 191 of them (82.6%) developed "single-site" irAEs and 40 (17.4%) "multiple-site" irAEs. At multivariate analysis, higher ORR was related to irAEs of any grade (P .0001), "single-site" irAEs (P .0001), endocrine (P = .0043) and skin irAEs (P = .0005). Longer PFS was related to irAEs of any grade (P .0001), "single-site" irAEs (P .0001), "multiple-site" irAEs (P = .0374), endocrine irAEs (P = .0084) and skin irAEs (P = .0001). Longer OS was related to irAEs of any grade (P .0001), "single-site" irAEs (P .0001), endocrine irAEs (P = .0044), gastrointestinal irAEs (P = .0437), skin irAEs (P = .0006), and others irAEs (P = .0378). At the 6-week landmark analysis, irAEs of any grade was confirmed an independent predictor of higher ORR, longer PFS, and longer OS.Our study confirmed that irAEs are concordantly related to higher ORR, longer PFS, and longer OS with anti-PD-1 immunotherapy in patients with NSCLC.
- Published
- 2019
32. Impact of primary tumor location in patients with RAS wild-type metastatic colon cancer treated with first-line chemotherapy plus anti-EGFR or anti-VEGF monoclonal antibodies: A retrospective multicenter study
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Matteo Neri, Antonino Grassadonia, Clara Natoli, Katia Cannita, Alessio Cortellini, Maddalena Barba, Pietro Di Marino, Corrado Ficorella, Federica Zoratto, Ettore Porreca, Nicola Tinari, Patrizia Vici, Angelo Veronese, Alessandro Parisi, Michele De Tursi, and Teresa Gamucci
- Subjects
Oncology ,medicine.medical_specialty ,Bevacizumab ,Colorectal cancer ,medicine.medical_treatment ,Cetuximab ,Targeted therapy ,Internal medicine ,medicine ,Panitumumab ,Chemotherapy ,business.industry ,medicine.disease ,Primary tumor ,Tumor location, Cetuximab, Panitumumab, Bevacizumab ,Tumor location ,Population study ,Metastatic colorectal cancer (mCRC) ,RAS wt ,business ,Research Paper ,medicine.drug - Abstract
Emerging evidence supports a prognostic role of primary tumor location in metastatic colon cancer (mCC). We conducted a retrospective analysis to evaluate the effect of tumor location on prognosis and efficacy of biological agents (anti-EGFR, Cetuximab and Panitumumab, or anti-VEGF, Bevacizumab) added to first-line chemotherapy in patients with RAS wild-type (wt) mCC. Patients with newly diagnosed RAS wt mCC candidates to first-line chemotherapy with anti-EGFRs or Bevacizumab were selected. Clinical outcomes were assessed and stratified by tumor location and type of treatment. Overall, 351 patients met the inclusion criteria. Primary colon cancer was right-sided (RCC) in 105 (29.9%) patients and left-sided (LCC) in 246 (70.1%). Patients with LCC had a better OS compared to those with RCC (33.6 vs 23.5 months, HR 0.74; 95% CI, 0.55 to 0.99; p=0.049). In the overall study population, OS was not significantly different for patients treated with Cetuximab or Panitumumab as compared to those receiving Bevacizumab. However, when comparing treatment outcome according to tumor sidedness, patients with LCC treated with Cetuximab or Panitumumab had a significantly longer PFS (12.4 vs 10.7 months; HR: 0.69; 95% CI, 0.51 to 0.93; p= 0.015) and OS (40.7 vs 28.6 months; HR: 0.67; 95% CI 0.47 to 0.95; p= 0.026). No relevant differences were observed in patients with RCC. We found evidence in support of the impact of tumor location in RAS wt mCC treated with first-line chemotherapy in association with targeted therapy. More favorable outcomes were observed in LCC patients, but not in RCC patients, treated with anti-EGFR agents compared with those who received Bevacizumab. Further, prospective and adequately sized studies are warranted to confirm our findings.
- Published
- 2019
33. Clinical Outcomes of Patients with Advanced Cancer and Pre-Existing Autoimmune Diseases Treated with Anti-Programmed Death-1 Immunotherapy: A Real-World Transverse Study
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Carlo Garufi, Antonino Grassadonia, Maria Giuseppa Vitale, Sergio Bracarda, Roberto Sabbatini, Tea Zeppola, Paolo A. Ascierto, Riccardo Marconcini, Andrea Botticelli, Marcello Tiseo, Cecilia Anesi, Giampiero Porzio, Raffaele Giusti, Gian Carlo Antonini Cappellini, Fabiana Perrone, Valeria Ciciarelli, Maria Concetta Fargnoli, Francesco Atzori, Sebastiano Buti, Enzo Veltri, Marco Filetti, Alessio Cortellini, Paolo Marchetti, Daniela Iacono, Michele De Tursi, Federica De Galitiis, Rossana Berardi, Annagrazia Pireddu, Davide Brocco, Melissa Bersanelli, Marianna Tudini, Rosa Rita Silva, Silvia Rinaldi, Federica Zoratto, Maria Rita Migliorino, Marco Russano, Antonio Rossi, Biagio Ricciuti, Katia Cannita, Francesco Malorgio, Maria Michiara, Rita Chiari, Daniele Santini, Nicola Tinari, and Corrado Ficorella
- Subjects
Adult ,Male ,0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Drug-Related Side Effects and Adverse Reactions ,medicine.medical_treatment ,Programmed Cell Death 1 Receptor ,Severity of Illness Index ,Autoimmune Diseases ,Young Adult ,03 medical and health sciences ,Immune checkpoint inhibitors ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Acquired immunodeficiency syndrome (AIDS) ,Neoplasms ,Internal medicine ,Autoimmune disease ,medicine ,Humans ,Anti-programmed death-1 ,Immunotherapy ,Performance status ,Sex ,Oncology ,Adverse effect ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Incidence ,Incidence (epidemiology) ,Middle Aged ,medicine.disease ,Immuno‐Oncology ,Progression-Free Survival ,Clinical trial ,030104 developmental biology ,030220 oncology & carcinogenesis ,Female ,business ,Kidney cancer - Abstract
BACKGROUND. Patients with a history of autoimmune diseases (AIDs) have not usually been included in clinical trials with immune checkpoint inhibitors. MATERIALS AND METHODS. Consecutive patients with advanced cancer, treated with anti‐programmed death‐1 (PD‐1) agents, were evaluated according to the presence of pre‐existing AIDs. The incidence of immune‐related adverse events (irAEs) and clinical outcomes were compared among subgroups. RESULTS. A total of 751 patients were enrolled; median age was 69 years. Primary tumors were as follows: non‐small cell lung cancer, 492 (65.5%); melanoma, 159 (21.2%); kidney cancer, 94 (12.5%); and others, 6 (0.8%). Male/female ratio was 499/252. Eighty‐five patients (11.3%) had pre‐existing AIDs, further differentiated in clinically active (17.6%) and inactive (82.4%). Among patients with pre‐existing AIDs, incidence of irAEs of any grade was significantly higher when compared with patients without AIDs (65.9% vs. 39.9%). At multivariate analysis, both inactive (p = .0005) and active pre‐existing AIDs (p = .0162), female sex (p = .0004), and Eastern Cooperative Oncology Group Performance Status
- Published
- 2019
34. Combination of peripheral neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio is predictive of pathological complete response after neoadjuvant chemotherapy in breast cancer patients
- Author
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Patrizia Vici, Laura Pizzuti, Vincenzo Graziano, Saverio Alberti, Clara Natoli, Pietro Di Marino, Mario Di Gioacchino, Antonino Grassadonia, Michele De Tursi, Annarita Camplese, Nicola Tinari, Maddalena Barba, Alberto Quinzii, Teresa Gamucci, Laura Iezzi, Serena Veschi, and Marta Peri
- Subjects
Oncology ,Adult ,Blood Platelets ,medicine.medical_specialty ,Neutrophils ,Lymphocyte ,medicine.medical_treatment ,Antineoplastic Agents ,Breast Neoplasms ,Logistic regression ,Disease-Free Survival ,03 medical and health sciences ,Leukocyte Count ,0302 clinical medicine ,Breast cancer ,Internal medicine ,Biomarkers, Tumor ,Medicine ,Humans ,030212 general & internal medicine ,Lymphocyte Count ,Lymphocytes ,Neutrophil to lymphocyte ratio ,Breast cancer, Neoadjuvant chemotherapy, Pathological complete response (pCR), Neutrophil to lymphocyte ratio (NLR), Platelet to lymphocyte ratio (PLR), Predictive factors ,Pathological ,Grading (tumors) ,Aged ,Retrospective Studies ,Chemotherapy ,business.industry ,fungi ,General Medicine ,Middle Aged ,medicine.disease ,Neoadjuvant Therapy ,body regions ,Exact test ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Surgery ,Female ,business - Abstract
The immune system seems to play a fundamental role in breast cancer responsiveness to chemotherapy. We investigated two peripheral indicators of immunity/inflammation, i.e. neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR), in order to reveal a possible relationship with pathological complete response (pCR) in patients with early or locally advanced breast cancer treated with neoadjuvant chemotherapy (NACT). We retrospectively analyzed 373 consecutive patients affected by breast cancer and candidates to NACT. The complete blood cell count before starting NACT was evaluated to calculate NLR and PLR. ROC curve analysis determined threshold values of 2.42 and 104.47 as best cut-off values for NLR and PLR, respectively. The relationships between NLR/PLR and pCR, along with other clinical-pathological characteristics, were evaluated by Pearson's χ 2 or Fisher's exact test as appropriate. Univariate and multivariate analyses were performed using a logistic regression model. NLR and PLR were not significantly associated with pCR if analyzed separately. However, when combining NLR and PLR, patients with a NLRlow/PLRlow profile achieved a significantly higher rate of pCR compared to those with NLRhigh and/or PLRhigh (OR 2.29, 95% CI 1.22-4.27, p 0.009). Importantly, the predictive value of NLRlow/PLRlow was independent from common prognostic factors such as grading, Ki67, and molecular subtypes. The combination of NLR and PLR may reflect patients' immunogenic phenotype. Low levels of both NLR and PLR may thus indicate a status of immune system activation that may predict pCR in breast cancer patients treated with NACT.
- Published
- 2018
35. Effect of Gender on the Outcome of Patients Receiving Immune Checkpoint Inhibitors for Advanced Cancer: A Systematic Review and Meta-Analysis of Phase III Randomized Clinical Trials
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Antonino Grassadonia, Clara Natoli, Michele De Tursi, Laura Iezzi, Maddalena Barba, Isabella Sperduti, Patrizia Vici, Teresa Gamucci, Gaetana Cognetti, Paolo Marchetti, Nicola Tinari, Marcello Maugeri-Saccà, Laura Pizzuti, and Davide Brocco
- Subjects
atezolizumab ,Oncology ,medicine.medical_specialty ,Durvalumab ,durvalumab ,lcsh:Medicine ,Ipilimumab ,Pembrolizumab ,Article ,law.invention ,immune checkpoint inhibitors ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Atezolizumab ,Internal medicine ,gender ,medicine ,sex ,030212 general & internal medicine ,ipilimumab ,oncology_oncogenics ,nivolumab ,business.industry ,Melanoma ,lcsh:R ,General Medicine ,medicine.disease ,anti-CTLA-4 ,030220 oncology & carcinogenesis ,Meta-analysis ,anti-PD-1/PDL-1 ,pembrolizumab ,Nivolumab ,business ,medicine.drug - Abstract
Evidence has recently emerged on the influence of gender on the immune system. In this systematic review and meta-analysis of phase III randomized clinical trials (RCTs), we explored the impact of gender on survival in patients with advanced cancer treated with immune checkpoint inhibitors (ICIs). We performed a comprehensive search of the literature updated to April 2018, including the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE. We extracted data on study characteristics and risk of bias in duplicate. Of 423 unique citations, 21 RCTs were included, inherently to 12,635 patients. Both males and females showed reduced risk of death associated with ICIs use (HR 0.73, p <, 0.001 and HR 0.77, p <, 0.001, respectively). Subgroup analyses by specific ICI showed similar OS in both genders for anti-PD-1/PDL-1. Anti-CTLA-4 use was associated with longer OS in men only (HR 0.77, p <, 0.012), with the exception of melanoma (in women, HR 0.80, p = 0.006). PFS was longer in men than in women (HR 0.67, p <, 0.001 and HR 0.77, p = 0.100, respectively). Conclusively, ICIs use was associated with more favorable outcomes in men, particularly for anti-CTLA-4 agents. In melanoma, not gender-related factors may influence the anti-tumor immune response evoked by ICIs.
- Published
- 2018
36. Body Mass Index and Treatment Outcomes in Metastatic Breast Cancer Patients Treated With Eribulin
- Author
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Patrizia Vici, M. Rinaldi, Franco Di Filippo, Letizia Perracchio, Luigi Di Lauro, Fiorentino Izzo, A. Vaccaro, Maddalena Barba, Andrea Michelotti, Laura Iezzi, Laura Pizzuti, Antonino Grassadonia, Antonio Giordano, E. Landucci, Clara Natoli, Marcello Maugeri-Saccà, Teresa Gamucci, Edoardo Pescarmona, Lucia Mentuccia, Domenico Sergi, Luca Moscetti, and Isabella Sperduti
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Physiology ,Clinical Biochemistry ,Estrogen receptor ,Overweight ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,Progression-free survival ,Survival analysis ,Proportional hazards model ,business.industry ,Cell Biology ,medicine.disease ,Metastatic breast cancer ,030104 developmental biology ,Endocrinology ,chemistry ,030220 oncology & carcinogenesis ,medicine.symptom ,business ,Body mass index ,Eribulin - Abstract
Eribulin has shown survival advantage and manageable toxicity in heavily pre-treated metastatic breast cancer (mBC). We assessed whether body mass index (BMI) impacts treatment outcomes in 101 patients treated with eribulin at six Italian Oncologic Centers. BMI was addressed as a categorical variable (18.5-24.9 vs. at least 25). Clinical benefit rate (CBR) was assessed overall and in subgroups defined by BMI, line of therapy (LOT), and hormone receptor (HR) status. Analysis of CBR by LOT and HR status were further stratified by BMI. Survival curves were compared using the Kaplan-Meier method and log-rank test. Predictors of survival were tested in Cox models. Patients treated with eribulin as third line showed greater CBR when their BMI was in the lowest category (77.8 vs. 58.1%, P = 0.03). Median progression free survival (PFS) and overall survival (OS) in normal and overweight patients were 4 (95% CI, 3-5) versus 3 (2.1-4) months, P = 0.02 and 13 (11-15) versus 12 (6-18) months, P = 0.96, respectively. Median PFS and OS in estrogen receptor (ER) positive and negative tumours were 4 (3-5) versus 3 (2-4) months, P = 0.005 and 14 (10-18) versus 7 (4-10), P = 0.02, respectively. In multivariate analyses, BMI impacted PFS at a nearly significant extent (P = 0.05), while ER expression significantly affected PFS and OS (P = 0.01 and 0.02, respectively). No relevant findings emerged concerning toxicity. We found evidence of greater efficacy of eribulin in leaner mBC patients, particularly if given as third line and in ER positive tumors. Further studies are warranted to confirm our findings.
- Published
- 2015
37. Is the skin a sanctuary for breast cancer cells during treatment with anti-HER2 antibodies?
- Author
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Antonino Grassadonia, Vincenzo Graziano, Maria Teresa Scognamiglio, Marinella Zilli, Clara Natoli, Patrizia Vici, and Jamara Giampietro
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,immune tolerance ,immune privilege ,Skin Neoplasms ,Receptor, ErbB-2 ,Biopsy ,Antineoplastic Agents ,Breast Neoplasms ,immune response ,Immune tolerance ,Breast cancer ,Immune system ,breast cancer ,Immune privilege ,Trastuzumab ,pertuzumab ,skin metastases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Humans ,skin and connective tissue diseases ,Neoplasm Staging ,Pharmacology ,Bedside to Bench Report ,business.industry ,Cancer ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Discontinuation ,Molecular Medicine ,Female ,Pertuzumab ,business ,Tomography, X-Ray Computed ,medicine.drug - Abstract
The occurrence of skin metastases is a common event in patients affected by advanced breast cancer, usually associated with systemic disease progression. Here we describe 2 cases of diffuse cutaneous metastases from HER2-overexpressing breast cancer occurring despite a dramatic response in liver and bone, respectively, during treatment with anti-HER2 antibodies Trastuzumab and Pertuzumab. We discuss the reasons for this discrepancy and suggest a possible implication of impaired immune response in the skin. Future research should provide strategies to overcome the induction of immune privilege in the skin in order to avoid discontinuation of effective treatments.
- Published
- 2015
38. Neoadjuvant Immune-Checkpoint Blockade in Triple-Negative Breast Cancer: Current Evidence and Literature-Based Meta-Analysis of Randomized Trials
- Author
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Eriseld Krasniqi, Nicola Tinari, Laura Pizzuti, Gennaro Ciliberto, Patrizia Vici, A. Fabbri, Isabella Sperduti, Clara Natoli, Maddalena Barba, Claudio Botti, Marco Mazzotta, Teresa Gamucci, Daniele Marinelli, Antonino Grassadonia, Silverio Tomao, Giuseppe Sanguineti, and A. Botticelli
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,lcsh:RC254-282 ,Article ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Breast cancer ,Randomized controlled trial ,Atezolizumab ,law ,Internal medicine ,medicine ,neoadjuvant therapy ,Neoadjuvant therapy ,Triple-negative breast cancer ,immune check point inhibitor ,business.industry ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Carboplatin ,Immune checkpoint ,meta-analysis ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,Meta-analysis ,triple-negative breast cancer ,business - Abstract
Chemotherapy based on the sequential use of anthracyclines and taxanes has long represented the most efficacious approach in the management of early-stage, triple-negative breast cancer, whose aggressive behavior is widely renowned. This standard chemotherapy backbone was subsequently enriched by the use of carboplatin, based on its association with increased pathologic complete response and efficacy in the metastatic setting. Following the results from the IMpassion130 trial, the recent approval of the immunotherapic agent atezolizumab in combination with chemotherapy as first-line treatment for programmed-death ligand 1-positive, unresectable locally advanced, or metastatic triple-negative breast cancer increasingly fueled the flourishing of trials of immune-checkpoint inhibitors in the early setting. In this work, we review the most recent inherent literature in light of key methodological issues and provide a quantitative summary of the results from phase II&ndash, III randomized trials of immunotherapic agents combined with chemotherapy in the setting of interest. Hints regarding future directions are also discussed.
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- 2020
39. The Role of Dysfunctional Adipose Tissue in Pancreatic Cancer: A Molecular Perspective
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Laura De Lellis, Antonino Grassadonia, Nicola Tinari, Serena Veschi, Davide Brocco, Alessandro Cama, and Rosalba Florio
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0301 basic medicine ,obesity ,Cancer Research ,pancreatic cancer ,Adipose tissue ,Adipokine ,Dysfunctional family ,Review ,Disease ,Malignancy ,Bioinformatics ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,Pancreatic cancer ,medicine ,business.industry ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Obesity ,adipose tissue ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,business ,Hormone - Abstract
Pancreatic cancer (PC) is a lethal malignancy with rising incidence and limited therapeutic options. Obesity is a well-established risk factor for PC development. Moreover, it negatively affects outcome in PC patients. Excessive fat accumulation in obese, over- and normal-weight individuals induces metabolic and inflammatory changes of adipose tissue microenvironment leading to a dysfunctional adipose “organ”. This may drive the association between abnormal fat accumulation and pancreatic cancer. In this review, we describe several molecular mechanisms that underpin this association at both local and systemic levels. We focus on the role of adipose tissue-derived circulating factors including adipokines, hormones and pro-inflammatory cytokines, as well as on the impact of the local adipose tissue in promoting PC. A discussion on potential therapeutic interventions, interfering with pro-tumorigenic effects of dysfunctional adipose tissue in PC, is included. Considering the raise of global obesity, research efforts to uncover the molecular basis of the relationship between pancreatic cancer and adipose tissue dysfunction may provide novel insights for the prevention of this deadly disease. In addition, these efforts may uncover novel targets for personalized interventional strategies aimed at improving the currently unsatisfactory PC therapeutic options.
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- 2020
40. Corrigendum to 'Circulating Cancer Stem Cell-Derived Extracellular Vesicles as a Novel Biomarker for Clinical Outcome Evaluation'
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Paola Lanuti, Maria Concetta Cufaro, P. Di Marino, P. Del Boccio, Antonino Grassadonia, Giuseppina Bologna, Marco Marchisio, Marta Peri, I. G. Rapposelli, Clara Natoli, Vincenzo Graziano, Laura Pierdomenico, Davide Brocco, Fausta Ciccocioppo, Paola Simeone, Sebastiano Miscia, Nicola Tinari, Damiana Pieragostino, M. De Tursi, Eva Ercolino, Grassadonia, A [0000-0002-2459-0661], Del Boccio, P [0000-0003-1653-2194], Marchisio, M [0000-0003-3058-3422], Natoli, C [0000-0001-7295-0230], and Apollo - University of Cambridge Repository
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business.industry ,education ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,32 Biomedical and Clinical Sciences ,3211 Oncology and Carcinogenesis ,Extracellular vesicles ,Oncology ,Cancer stem cell ,Cancer research ,Biomarker (medicine) ,Medicine ,Corrigendum ,business ,RC254-282 - Abstract
[This corrects the article DOI: 10.1155/2019/5879616.].
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- 2020
41. Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial
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Sabino De Placido, Ciro Gallo, Michelino De Laurentiis, Giancarlo Bisagni, Grazia Arpino, Maria Giuseppa Sarobba, Ferdinando Riccardi, Antonio Russo, Lucia Del Mastro, Alessio Aligi Cogoni, Francesco Cognetti, Stefania Gori, Jennifer Foglietta, Antonio Frassoldati, Domenico Amoroso, Lucio Laudadio, Luca Moscetti, Filippo Montemurro, Claudio Verusio, Antonio Bernardo, Vito Lorusso, Adriano Gravina, Gabriella Moretti, Rossella Lauria, Antonella Lai, Carmela Mocerino, Sergio Rizzo, Francesco Nuzzo, Paolo Carlini, Francesco Perrone, Antonello Accurso, Biagio Agostara, Michele Aieta, Oscar Alabiso, Maria Grazia Alicicco, Dino Amadori, Laura Amaducci, Gianna Amiconi, Giustino Antuzzi, Mara Ardine, Antonio Ardizzoia, Caterina Aversa, Giuseppe Badalamenti, Sandro Barni, Carlo Basurto, Rossana Berardi, Cinzia Bergamasco, Paolo Bidoli, Claudia Bighin, Edoardo Biondi, Corrado Boni, Karen Borgonovo, Mario Botta, Stefano Bravi, Paolo Bruzzi, Giuseppe Buono, Alfredo Butera, Alessia Caldara, Giampiero Candeloro, Claudia Cappelletti, Cinzia Cardalesi, Elisabetta Carfora, Anna Cariello, Francesco Carrozza, Giacomo Cartenì, Michele Caruso, Virginia Casadei, Claudia Casanova, Luigi Castori, Luigi Cavanna, Giovanna Cavazzini, Marina Cazzaniga, Mario Chilelli, Paolo Chiodini, Silvia Chiorrini, Fortunato Ciardiello, Mariangela Ciccarese, Saverio Cinieri, Mario Clerico, Mariarosa Coccaro, Mario Comande, Claudia Corbo, Giuseppina Cortino, Stefania Cusenza, Gennaro Daniele, Alfonso Maria D'arco, Giuliana D'auria, Claudio Dazzi, Carmine De Angelis, Filippo de Braud, Gianfranco De Feo, Andrea De Matteis, Michele De Tursi, Anna Di Blasio, Giuseppe di Lucca, Liberato Di Lullo, Francesca Di Rella, Gianfranco Di Renzo, Pia Di Stefano, Aida Di Stefano, Anna Diana, Sara Donati, Agnese Fabbri, Alessandra Fabi, Marina Faedi, Gabriella Farina, Antonio Farris, Antonio Febbraro, Palma Fedele, Piera Federico, Francesco Ferraù, Gianluigi Ferretti, Antonella Ferro, Irene Floriani, Rosachiara Forcignanò, Samantha Forciniti, Valeria Forestieri, Gianni Fornari, Michela Frisinghelli, Vittorio Fusco, Giulia Gallizzi, Antonio Galvano, Antonio Gambardella, Angelo Gambi, Vittorio Gebbia, Erika Gervasi, Mara Ghilardi, Alice Giacobino, Giovanni Giardina, Francesco Giotta, Sara Giraudi, Mario Giuliano, Antonino Grassadonia, Donatella Grasso, Federica Grosso, Lorenzo Guizzaro, Pasquale Incoronato, Lorena Incorvaia, Giovanni Iodice, Nicla La Verde, Vincenzo Labonia, Gabriella Landi, Agnese Latorre, Vita Leonardi, Alessia Levaggi, Gennaro Limite, Linda Lina Bascialla, Lorenzo Livi, Evaristo Maiello, Daniela Mandelli, Ilaria Marcon, Daniela Menon, Michele Montedoro, Lucia Moraca, Anna Moretti, Maria Grazia Morritti, Patrizia Morselli, Antonella Mura, Silvia Mura, Michela Musacchio, Alberto Muzio, Donato Natale, Clara Natoli, Cinzia Nigro, Cecilia Nisticò, Antonio Nuzzo, Michele Orditura, Laura Orlando, Carmen Pacilio, Giuliano Palumbo, Raffaella Palumbo, Felice Pasini, Emanuela Paterno, Antonio Pazzola, Silvia Pelliccioni, Matilde Pensabene, Davide Perroni, Angela Pesenti Gritti, Fausto Petrelli, Maria Carmela Piccirillo, Graziella Pinotti, Claudia Pogliani, Davide Poli, Sonia Prader, Francesco Recchia, Daniele Rizzi, Carmen Romano, Rosalba Rossello, Chiara Rossini, Giuseppina Salvucci, Valeria Sanna, Alessandra Santini, Silvana Saracchini, Clementina Savastano, Giovanni Scambia, Francesco Schettini, Paola Schiavone, Alessio Schirone, Elena Seles, Simona Signoriello, Giuseppe Signoriello, Rosa Rita Silva, Antonia Silvestri, Vittorio Simeon, Ilaria Spagnoletti, Stefano Tamberi, Cristina Teragni, Verena Thalmann, Renato Thomas, Guglielmo Thomas, Amelia Tienghi, Nicola Tinari, Vincenza Tinessa, Federica Tomei, Giuseppe Tonini, Valter Torri, Divina Traficante, Marianna Tudini, Monica Turazza, Roberto Vignoli, Maria Giuseppa Vitale, Alessandra Zacchia, Pasquale Zagarese, Alda Zanni, Laura Zavallone, Maria Zavettieri, Alessandra Zoboli, De Placido, S., Gallo, C., De Laurentiis, M., Bisagni, G., Arpino, G., Sarobba, M. G., Riccardi, F., Russo, A., Del Mastro, L., Cogoni, A. A., Cognetti, F., Gori, S., Foglietta, J., Frassoldati, A., Amoroso, D., Laudadio, L., Moscetti, L., Montemurro, F., Verusio, C., Bernardo, A., Lorusso, V., Gravina, A., Moretti, G., Lauria, R., Lai, A., Mocerino, C., Rizzo, S., Nuzzo, F., Carlini, P., Perrone, F., Accurso, A., Agostara, B., Aieta, M., Alabiso, O., Alicicco, M. G., Amadori, D., Amaducci, L., Amiconi, G., Antuzzi, G., Ardine, M., Ardizzoia, A., Aversa, C., Badalamenti, G., Barni, S., Basurto, C., Berardi, R., Bergamasco, C., Bidoli, P., Bighin, C., Biondi, E., Boni, C., Borgonovo, K., Botta, M., Bravi, S., Bruzzi, P., Buono, G., Butera, A., Caldara, A., Candeloro, G., Cappelletti, C., Cardalesi, C., Carfora, E., Cariello, A., Carrozza, F., Carteni, G., Caruso, M., Casadei, V., Casanova, C., Castori, L., Cavanna, L., Cavazzini, G., Cazzaniga, M., Chilelli, M., Chiodini, P., Chiorrini, S., Ciardiello, F., Ciccarese, M., Cinieri, S., Clerico, M., Coccaro, M., Comande, M., Corbo, C., Cortino, G., Cusenza, S., Daniele, G., D'Arco, A. M., D'Auria, G., Dazzi, C., De Angelis, C., de Braud, F., De Feo, G., De Matteis, Ma., De Tursi, M., Di Blasio, A., di Lucca, G., Di Lullo, L., Di Rella, F., Di Renzo, G., Di Stefano, P., Di Stefano, A., Diana, A., Donati, S., Fabbri, A., Fabi, A., Faedi, M., Farina, G., Farris, A., Febbraro, A., Fedele, P., Federico, P., Ferrau, F., Ferretti, G., Ferro, A., Floriani, I., Forcignano, R., Forciniti, S., Forestieri, V., Fornari, G., Frisinghelli, M., Fusco, V., Gallizzi, G., Galvano, A., Gambardella, A., Gambi, A., Gebbia, V., Gervasi, E., Ghilardi, M., Giacobino, A., Giardina, G., Giotta, F., Giraudi, S., Giuliano, M., Grassadonia, A., Grasso, D., Grosso, F., Guizzaro, L., Incoronato, P., Incorvaia, L., Iodice, G., La Verde, N., Labonia, V., Landi, G., Latorre, A., Leonardi, V., Levaggi, A., Limite, G., Lina Bascialla, L., Livi, L., Maiello, E., Mandelli, D., Marcon, I., Menon, D., Montedoro, M., Moraca, L., Moretti, A., Morritti, M. G., Morselli, P., Mura, A., Mura, S., Musacchio, M., Muzio, A., Natale, D., Natoli, C., Nigro, C., Nistico, C., Nuzzo, A., Orditura, M., Orlando, L., Pacilio, C., Palumbo, G., Palumbo, R., Pasini, F., Paterno, E., Pazzola, A., Pelliccioni, S., Pensabene, M., Perroni, D., Pesenti Gritti, A., Petrelli, F., Piccirillo, M. C., Pinotti, G., Pogliani, C., Poli, D., Prader, S., Recchia, F., Rizzi, D., Romano, C., Rossello, R., Rossini, C., Salvucci, G., Sanna, V., Santini, A., Saracchini, S., Savastano, C., Scambia, G., Schettini, F., Schiavone, P., Schirone, A., Seles, E., Signoriello, S., Signoriello, G., Silva, R. R., Silvestri, A., Simeon, V., Spagnoletti, I., Tamberi, S., Teragni, C., Thalmann, V., Thomas, R., Thomas, G., Tienghi, A., Tinari, N., Tinessa, V., Tomei, F., Tonini, G., Torri, V., Traficante, D., Tudini, M., Turazza, M., Vignoli, R., Vitale, M. G., Zacchia, A., Zagarese, P., Zanni, A., Zavallone, L., Zavettieri, M., Zoboli, A., De Placido, Sabino, Gallo, Ciro, De Laurentiis, Michelino, Bisagni, Giancarlo, Arpino, Grazia, Sarobba, Maria Giuseppa, Riccardi, Ferdinando, Russo, Antonio, Del Mastro, Lucia, Cogoni, Alessio Aligi, Cognetti, Francesco, Gori, Stefania, Foglietta, Jennifer, Frassoldati, Antonio, Amoroso, Domenico, Laudadio, Lucio, Moscetti, Luca, Montemurro, Filippo, Verusio, Claudio, Bernardo, Antonio, Lorusso, Vito, Gravina, Adriano, Moretti, Gabriella, Lauria, Rossella, Lai, Antonella, Mocerino, Carmen, Rizzo, Sergio, Nuzzo, Francesco, Carlini, Paolo, Perrone, Francesco, Accurso, Antonello, Agostara, Biagio, Aieta, Michele, Alabiso, Oscar, Alicicco, Maria Grazia, Amadori, Dino, Amaducci, Laura, Amiconi, Gianna, Antuzzi, Giustino, Ardine, Mara, Ardizzoia, Antonio, Aversa, Caterina, Badalamenti, Giuseppe, Barni, Sandro, Basurto, Carlo, Berardi, Rossana, Bergamasco, Cinzia, Bidoli, Paolo, Bighin, Claudia, Biondi, Edoardo, Boni, Corrado, Borgonovo, Karen, Botta, Mario, Bravi, Stefano, Bruzzi, Paolo, Buono, Giuseppe, Butera, Alfredo, Caldara, Alessia, Candeloro, Giampiero, Cappelletti, Claudia, Cardalesi, Cinzia, Carfora, Elisabetta, Cariello, Anna, Carrozza, Francesco, Cartenì, Giacomo, Caruso, Michele, Casadei, Virginia, Casanova, Claudia, Castori, Luigi, Cavanna, Luigi, Cavazzini, Giovanna, Cazzaniga, Marina, Chilelli, Mario, Chiodini, Paolo, Chiorrini, Silvia, Ciardiello, Fortunato, Ciccarese, Mariangela, Cinieri, Saverio, Clerico, Mario, Coccaro, Mariarosa, Comande, Mario, Corbo, Claudia, Cortino, Giuseppina, Cusenza, Stefania, Daniele, Gennaro, D'arco, Alfonso Maria, D'auria, Giuliana, Dazzi, Claudio, De Angelis, Carmine, de Braud, Filippo, De Feo, Gianfranco, De Matteis, Andrea, De Tursi, Michele, Di Blasio, Anna, di Lucca, Giuseppe, Di Lullo, Liberato, Di Rella, Francesca, Di Renzo, Gianfranco, Di Stefano, Pia, Di Stefano, Aida, Diana, Anna, Donati, Sara, Fabbri, Agnese, Fabi, Alessandra, Faedi, Marina, Farina, Gabriella, Farris, Antonio, Febbraro, Antonio, Fedele, Palma, Federico, Piera, Ferraù, Francesco, Ferretti, Gianluigi, Ferro, Antonella, Floriani, Irene, Forcignanò, Rosachiara, Forciniti, Samantha, Forestieri, Valeria, Fornari, Gianni, Frisinghelli, Michela, Fusco, Vittorio, Gallizzi, Giulia, Galvano, Antonio, Gambardella, Antonio, Gambi, Angelo, Gebbia, Vittorio, Gervasi, Erika, Ghilardi, Mara, Giacobino, Alice, Giardina, Giovanni, Giotta, Francesco, Giraudi, Sara, Giuliano, Mario, Grassadonia, Antonino, Grasso, Donatella, Grosso, Federica, Guizzaro, Lorenzo, Incoronato, Pasquale, Incorvaia, Lorena, Iodice, Giovanni, La Verde, Nicla, Labonia, Vincenzo, Landi, Gabriella, Latorre, Agnese, Leonardi, Vita, Levaggi, Alessia, Limite, Gennaro, Lina Bascialla, Linda, Livi, Lorenzo, Maiello, Evaristo, Mandelli, Daniela, Marcon, Ilaria, Menon, Daniela, Montedoro, Michele, Moraca, Lucia, Moretti, Anna, Morritti, Maria Grazia, Morselli, Patrizia, Mura, Antonella, Mura, Silvia, Musacchio, Michela, Muzio, Alberto, Natale, Donato, Natoli, Clara, Nigro, Cinzia, Nisticò, Cecilia, Nuzzo, Antonio, Orditura, Michele, Orlando, Laura, Pacilio, Carmen, Palumbo, Giuliano, Palumbo, Raffaella, Pasini, Felice, Paterno, Emanuela, Pazzola, Antonio, Pelliccioni, Silvia, Pensabene, Matilde, Perroni, Davide, Pesenti Gritti, Angela, Petrelli, Fausto, Piccirillo, Maria Carmela, Pinotti, Graziella, Pogliani, Claudia, Poli, Davide, Prader, Sonia, Recchia, Francesco, Rizzi, Daniele, Romano, Carmen, Rossello, Rosalba, Rossini, Chiara, Salvucci, Giuseppina, Sanna, Valeria, Santini, Alessandra, Saracchini, Silvana, Savastano, Clementina, Scambia, Giovanni, Schettini, Francesco, Schiavone, Paola, Schirone, Alessio, Seles, Elena, Signoriello, Simona, Signoriello, Giuseppe, Silva, Rosa Rita, Silvestri, Antonia, Simeon, Vittorio, Spagnoletti, Ilaria, Tamberi, Stefano, Teragni, Cristina, Thalmann, Verena, Thomas, Renato, Thomas, Guglielmo, Tienghi, Amelia, Tinari, Nicola, Tinessa, Vincenza, Tomei, Federica, Tonini, Giuseppe, Torri, Valter, Traficante, Divina, Tudini, Marianna, Turazza, Monica, Vignoli, Roberto, Vitale, Maria Giuseppa, Zacchia, Alessandra, Zagarese, Pasquale, Zanni, Alda, Zavallone, Laura, Zavettieri, Maria, Zoboli, Alessandra, Mocerino, Carmela, D'Arco, Alfonso Maria, D'Auria, Giuliana, De Placido, S, Gallo, C, De Laurentiis, M, Bisagni, G, Arpino, G, Sarobba, M, Riccardi, F, Russo, A, Del Mastro, L, Cogoni, A, Cognetti, F, Gori, S, Foglietta, J, Frassoldati, A, Amoroso, D, Laudadio, L, Moscetti, L, Montemurro, F, Verusio, C, Bernardo, A, Lorusso, V, Gravina, A, Moretti, G, Lauria, R, Lai, A, Mocerino, C, Rizzo, S, Nuzzo, F, Carlini, P, Perrone, F, Accurso, A, Agostara, B, Aieta, M, Alabiso, O, Alicicco, M, Amadori, D, Amaducci, L, Amiconi, G, Antuzzi, G, Ardine, M, Ardizzoia, A, Aversa, C, Badalamenti, G, Barni, S, Basurto, C, Berardi, R, Bergamasco, C, Bidoli, P, Bighin, C, Biondi, E, Boni, C, Borgonovo, K, Botta, M, Bravi, S, Bruzzi, P, Buono, G, Butera, A, Caldara, A, Candeloro, G, Cappelletti, C, Cardalesi, C, Carfora, E, Cariello, A, Carrozza, F, Carteni, G, Caruso, M, Casadei, V, Casanova, C, Castori, L, Cavanna, L, Cavazzini, G, Cazzaniga, M, Chilelli, M, Chiodini, P, Chiorrini, S, Ciardiello, F, Ciccarese, M, Cinieri, S, Clerico, M, Coccaro, M, Comande, M, Corbo, C, Cortino, G, Cusenza, S, Daniele, G, D'Arco, A, D'Auria, G, Dazzi, C, De Angelis, C, de Braud, F, De Feo, G, De Matteis, A, De Tursi, M, Di Blasio, A, di Lucca, G, Di Lullo, L, Di Rella, F, Di Renzo, G, Di Stefano, P, Di Stefano, A, Diana, A, Donati, S, Fabbri, A, Fabi, A, Faedi, M, Farina, G, Farris, A, Febbraro, A, Fedele, P, Federico, P, Ferrau, F, Ferretti, G, Ferro, A, Floriani, I, Forcignano, R, Forciniti, S, Forestieri, V, Fornari, G, Frisinghelli, M, Fusco, V, Gallizzi, G, Galvano, A, Gambardella, A, Gambi, A, Gebbia, V, Gervasi, E, Ghilardi, M, Giacobino, A, Giardina, G, Giotta, F, Giraudi, S, Giuliano, M, Grassadonia, A, Grasso, D, Grosso, F, Guizzaro, L, Incoronato, P, Incorvaia, L, Iodice, G, La Verde, N, Labonia, V, Landi, G, Latorre, A, Leonardi, V, Levaggi, A, Limite, G, Lina Bascialla, L, Livi, L, Maiello, E, Mandelli, D, Marcon, I, Menon, D, Montedoro, M, Moraca, L, Moretti, A, Morritti, M, Morselli, P, Mura, A, Mura, S, Musacchio, M, Muzio, A, Natale, D, Natoli, C, Nigro, C, Nistico, C, Nuzzo, A, Orditura, M, Orlando, L, Pacilio, C, Palumbo, G, Palumbo, R, Pasini, F, Paterno, E, Pazzola, A, Pelliccioni, S, Pensabene, M, Perroni, D, Pesenti Gritti, A, Petrelli, F, Piccirillo, M, Pinotti, G, Pogliani, C, Poli, D, Prader, S, Recchia, F, Rizzi, D, Romano, C, Rossello, R, Rossini, C, Salvucci, G, Sanna, V, Santini, A, Saracchini, S, Savastano, C, Scambia, G, Schettini, F, Schiavone, P, Schirone, A, Seles, E, Signoriello, S, Signoriello, G, Silva, R, Silvestri, A, Simeon, V, Spagnoletti, I, Tamberi, S, Teragni, C, Thalmann, V, Thomas, R, Thomas, G, Tienghi, A, Tinari, N, Tinessa, V, Tomei, F, Tonini, G, Torri, V, Traficante, D, Tudini, M, Turazza, M, Vignoli, R, Vitale, M, Zacchia, A, Zagarese, P, Zanni, A, Zavallone, L, Zavettieri, M, and Zoboli, A
- Subjects
Oncology ,Receptor, ErbB-2 ,Settore MED/06 - Oncologia Medica ,letrozole ,law.invention ,Adjuvant anastrozole ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,Exemestane ,law ,exemestane ,tamoxifen ,breast cancer ,Antineoplastic Combined Chemotherapy Protocols ,030212 general & internal medicine ,Aromatase Inhibitors ,Letrozole ,Hazard ratio ,Middle Aged ,Receptors, Estrogen ,Tolerability ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Female ,Receptors, Progesterone ,Breast Neoplasm ,Human ,medicine.drug ,medicine.medical_specialty ,Socio-culturale ,Anastrozole ,Breast Neoplasms ,Disease-Free Survival ,Drug Administration Schedule ,03 medical and health sciences ,Breast cancer ,Internal medicine ,medicine ,Aromatase Inhibitor ,Humans ,Aged ,Antineoplastic Combined Chemotherapy Protocol ,Androstadiene ,business.industry ,medicine.disease ,Androstadienes ,chemistry ,business ,Tamoxifen - Abstract
Background: Uncertainty exists about the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors and, to our knowledge, no trial has directly compared the three aromatase inhibitors anastrozole, exemestane, and letrozole. We investigated the schedule and type of aromatase inhibitors to be used as adjuvant treatment for hormone receptor-positive early breast cancer. Methods: FATA-GIM3 is a multicentre, open-label, randomised, phase 3 trial of six different treatments in postmenopausal women with hormone receptor-positive early breast cancer. Eligible patients had histologically confirmed invasive hormone receptor-positive breast cancer that had been completely removed by surgery, any pathological tumour size, and axillary nodal status. Key exclusion criteria were hormone replacement therapy, recurrent or metastatic disease, previous treatment with tamoxifen, and another malignancy in the previous 10 years. Patients were randomly assigned in an equal ratio to one of six treatment groups: oral anastrozole (1 mg per day), exemestane (25 mg per day), or letrozole (2·5 mg per day) tablets upfront for 5 years (upfront strategy) or oral tamoxifen (20 mg per day) for 2 years followed by oral administration of one of the three aromatase inhibitors for 3 years (switch strategy). Randomisation was done by a computerised minimisation procedure stratified for oestrogen receptor, progesterone receptor, and HER2 status; previous chemotherapy; and pathological nodal status. Neither the patients nor the physicians were masked to treatment allocation. The primary endpoint was disease-free survival. The minimum cutoff to declare superiority of the upfront strategy over the switch strategy was assumed to be a 2% difference in disease-free survival at 5 years. Primary efficacy analyses were done by intention to treat; safety analyses included all patients for whom at least one safety case report form had been completed. Follow-up is ongoing. This trial is registered with the European Clinical Trials Database, number 2006-004018-42, and ClinicalTrials.gov, number NCT00541086. Findings: Between March 9, 2007, and July 31, 2012, 3697 patients were enrolled into the study. After a median follow-up of 60 months (IQR 46â72), 401 disease-free survival events were reported, including 211 (11%) of 1850 patients allocated to the switch strategy and 190 (10%) of 1847 patients allocated to upfront treatment. 5-year disease-free survival was 88·5% (95% CI 86·7â90·0) with the switch strategy and 89·8% (88·2â91·2) with upfront treatment (hazard ratio 0·89, 95% CI 0·73â1·08; p=0·23). 5-year disease-free survival was 90·0% (95% CI 87·9â91·7) with anastrozole (124 events), 88·0% (85·8â89·9) with exemestane (148 events), and 89·4% (87·3 to 91·1) with letrozole (129 events; p=0·24). No unexpected serious adverse reactions or treatment-related deaths occurred. Musculoskeletal side-effects were the most frequent grade 3â4 events, reported in 130 (7%) of 1761 patients who received the switch strategy and 128 (7%) of 1766 patients who received upfront treatment. Grade 1 musculoskeletal events were more frequent with the upfront schedule than with the switch schedule (924 [52%] of 1766 patients vs 745 [42%] of 1761 patients). All other grade 3â4 adverse events occurred in less than 2% of patients in either group. Interpretation: 5 years of treatment with aromatase inhibitors was not superior to 2 years of tamoxifen followed by 3 years of aromatase inhibitors. None of the three aromatase inhibitors was superior to the others in terms of efficacy. Therefore, patient preference, tolerability, and financial constraints should be considered when deciding the optimal treatment approach in this setting. Funding: Italian Drug Agency.
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- 2018
42. Body mass index in HER2-negative metastatic breast cancer treated with first-line paclitaxel and bevacizumab
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Domenico Sergi, A. Vaccaro, Patrizia Vici, Valentina Sini, I. Bertolini, Antonino Grassadonia, Claudio Botti, Silverio Tomao, Isabella Sperduti, Marco Mazzotta, Fiorentino Izzo, Laura Pizzuti, Antonio Astone, Paolo Marchetti, Luca Marchetti, Gennaro Ciliberto, Emanuela Magnolfi, Teresa Gamucci, Ernesto Rossi, Luigi Di Lauro, Andrea Botticelli, Andrea Michelotti, Lucia Mentuccia, M.G. Sarobba, Clara Natoli, Marcello Maugeri-Saccà, Maria Agnese Fabbri, Claudia De Angelis, Antonio Giordano, Luca Moscetti, Francesco Angelini, Maddalena Barba, and Alessandra Cassano
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0301 basic medicine ,Oncology ,Cancer Research ,Receptor, ErbB-2 ,receptor ,0302 clinical medicine ,ErbB-2 ,middle aged ,80 and over ,breast neoplasms ,HER2-negative metastatic breast cancer ,Prospective cohort study ,humans ,Bevacizumab-including regimens ,Aged, 80 and over ,adult ,Metastatic breast cancer ,Research Papers ,Bevacizumab ,aged ,female ,030220 oncology & carcinogenesis ,Cohort ,Population study ,BMI ,first-line treatment ,triple negative subtype ,aged, 80 and over ,antineoplastic combined chemotherapy protocols ,Kaplan-Meier estimate ,Paclitaxel ,progression-free survival ,receptor, ErbB-2 ,body mass index ,Molecular Medicine ,medicine.drug ,medicine.medical_specialty ,Pharmacology ,03 medical and health sciences ,Internal medicine ,medicine ,Progression-free survival ,Settore MED/06 - ONCOLOGIA MEDICA ,business.industry ,Cancer ,medicine.disease ,030104 developmental biology ,business ,Body mass index - Abstract
The evidence emerged from the TOURANDOT trial encourages evaluating the role of anthropometric determinants on treatment outcomes in HER2-negative metastatic breast cancer patients treated with bevacizumab-including regimens. We thus analyzed data from a subgroup of these patients from a larger cohort previously assessed for treatment outcomes. Patients were included in the present analysis if body mass index values had been recorded at baseline. Clinical benefit rates, progression free survival and overall survival were assessed for the overall study population and subgroups defined upon molecular subtype. One hundred ninety six patients were included (N:196). Body mass index showed no impact on clinical benefit rates in the overall study sample and in the luminal cancer subset (p = 0.12 and p = 0.79, respectively), but did so in the triple negative subgroup, with higher rates in patients with body mass index ≥25 (p = 0.03). In the overall study sample, body mass index did no impact progression free or overall survival (p = 0.33 and p = 0.67, respectively). Conversely, in triple negative patients, progression free survival was significantly longer with body mass index ≥25 (6 vs 14 months, p = 0.04). In this subset, overall survival was more favorable (25 vs 19 months, p = 0.02). The impact of the molecular subtype was confirmed in multivariate models including the length of progression free survival, and number of metastatic sites (p < 0.0001). Further studies are warranted to confirm our findings in more adequately sized, ad hoc, prospective studies.
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- 2018
43. Identification of Subgroups of Early Breast Cancer Patients at High Risk of Nonadherence to Adjuvant Hormone Therapy: Results of an Italian Survey
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Elisabetta Gambale, Lorenzo Mazzilli, Teresa Gamucci, Maria Agnese Fabbri, Antonio Nuzzo, M. Mauri, Ettore Cianchetti, Antonino Grassadonia, Stefania Gori, Silvia Ileana Fattoruso, Marilena Romero, Caterina Fanizza, Flavia Longo, Clara Natoli, Luca Moscetti, A. Vaccaro, Lucio Laudadio, Patrizia Seminara, Patrizia Vici, and Nicola Tinari
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Breast Cancer ,Hormonal Adjuvant Therapy ,nonadherence to therapy ,medicine.medical_specialty ,Cancer Research ,Multivariate analysis ,Antineoplastic Agents, Hormonal ,medicine.drug_class ,medicine.medical_treatment ,Oral drugs ,Breast Neoplasms ,Logistic regression ,Adherence to therapy ,Breast cancer ,Adjuvant endocrine therapy ,Recursive partitioning and amalgamation analysis ,Risk Factors ,Internal medicine ,Surveys and Questionnaires ,Medicine ,Humans ,Aged ,Aromatase inhibitor ,business.industry ,Cancer ,Middle Aged ,medicine.disease ,Clinical trial ,Italy ,Oncology ,Chemotherapy, Adjuvant ,Physical therapy ,Patient Compliance ,Female ,Hormone therapy ,business ,Tamoxifen ,medicine.drug - Abstract
Background Adherence to adjuvant endocrine therapy (HT) is suboptimal among breast cancer patients. A high rate of nonadherence might explain differences in survival between clinical trial and clinical practice. Tailored interventions aimed at improving adherence can only be implemented if subgroups of patients at higher risk of poor adherence are identified. Because no data are available for Italy, we undertook a large survey on adherence among women taking adjuvant HT for breast cancer. Patients and Methods Patients were recruited from 10 cancer clinics in central Italy. All patients taking HT for at least 1 year were invited, during one of their follow-up visit, to fill a confidential questionnaire. The association of sociodemographic and clinical characteristics of participants with adherence was assessed using logistic regression. The RECPAM method was used to evaluate interactions among variables and to identify subgroups of patients at different risk of nonadherence. Results A total of 939 patients joined the study and 18.6% of them were classified as nonadherers. Among possible predictors, only age, working status, and switching from tamoxifen to an aromatase inhibitor were predictive of nonadherence in multivariate analysis. RECPAM analysis led to the identification of 4 classes of patients with a different likelihood of nonadherence to therapy, the lowest being observed in retired women with a low level of education, the highest in the group of unmarried, employed women, or housewives. Conclusion The identification of these subgroups of “real life” patients with a high prevalence of nonadherers might be functional in designing intervention studies aimed at improving adherence.
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- 2015
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44. Effect of Targeted Agents on the Endocrine Response of Breast Cancer in the Neoadjuvant Setting: A Systematic Review
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Patrizia Vici, Marta Caporale, Michele DeTursi, Marinella Zilli, Teresa Gamucci, Clara Natoli, Antonino Grassadonia, and Nicola Tinari
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Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Anastrozole ,Review ,clinical response ,Lapatinib ,Bioinformatics ,neoadjuvant endocrine therapy ,Targeted therapy ,chemistry.chemical_compound ,breast cancer ,Breast cancer ,Exemestane ,Internal medicine ,medicine ,Everolimus ,business.industry ,Letrozole ,Cancer ,targeted therapy ,medicine.disease ,chemistry ,business ,medicine.drug - Abstract
Inhibition of aberrantly activated pathways cross-talking with hormone receptor (HR) improves response to endocrine therapy in patients with HR-positive advanced breast cancer. We performed a Pubmed database systematic review to ascertain the existence of a better clinical response when combining endocrine therapy with targeted agents in the neoadjuvant setting. Preclinical studies or trials evaluating toxicity were excluded. We found nine phase II trials that fulfilled the research criteria. The endocrine agents used were third generation aromatase inhibitors (AIs), anastrozole, letrozole or exemestane. The investigated targeted agents were inhibitors of tyrosine kinase receptors such as gefitinib, imatinib or trastuzumab/lapatinib, inhibitors of mTOR, such as everolimus, inhibitors of COX-2, such as celecoxib, and inhibitors of angiogenesis, such as bevacizumab. The response rate (RR) observed combining endocrine and targeted agents ranged between 36% and 90%. Overall the studies failed to show a remarkable advantage in RR in the combination group compared to historical control subjects receiving AIs alone.
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- 2015
45. Reply to Kadri Altundag: Do cut-off values of lymph node ratio and presence of perineural invasion affect survival in breast cancer patients with pathologic N3a lymph node stage?
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Teresa Gamucci, Jamara Giampietro, Vincenzo Graziano, Marinella Zilli, Patrizia Vici, Clara Natoli, Laura Iezzi, Laura Pizzuti, Lucia Mentuccia, Antonino Grassadonia, Nicola Tinari, Maria Teresa Scognamiglio, and Luca Moscetti
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Oncology ,medicine.medical_specialty ,Lymphatic metastasis ,business.industry ,Perineural invasion ,Breast Neoplasms ,General Medicine ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Internal medicine ,Lymphatic Metastasis ,medicine ,Humans ,030211 gastroenterology & hepatology ,Surgery ,Lymph Nodes ,Stage (cooking) ,business ,Lymph node - Published
- 2017
46. Inhibition of Tumor Growth and Angiogenesis by SP-2, an Anti–Lectin, Galactoside-Binding Soluble 3 Binding Protein (LGALS3BP) Antibody
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Enza Piccolo, Anna Bagnato, Mauro Piantelli, Antonino Grassadonia, Nicola Tinari, Rossano Lattanzio, Stefano Iacobelli, Rossana La Sorda, Sara Traini, Francesca Spinella, Federica Tomao, Clara Natoli, Annalisa Di Risio, Cosmo Rossi, and Maurizia D'Egidio
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Cancer Research ,Angiogenesis ,Mice, Nude ,Antineoplastic Agents ,Biology ,Antibodies, Monoclonal, Humanized ,Mice ,Antigens, Neoplasm ,In vivo ,Cell Line, Tumor ,Neoplasms ,Antineoplastic Combined Chemotherapy Protocols ,Biomarkers, Tumor ,Human Umbilical Vein Endothelial Cells ,Animals ,Humans ,Protein kinase B ,Glycoproteins ,Binding protein ,Antibodies, Monoclonal ,Mammary Neoplasms, Experimental ,Drug Synergism ,Xenograft Model Antitumor Assays ,Molecular biology ,Bevacizumab ,Endothelial stem cell ,Oncology ,Galactoside binding ,Cancer research ,biology.protein ,Phosphorylation ,Female ,Antibody ,Carrier Proteins - Abstract
Accumulating evidence indicates that serum and tissue levels of lectin, galactoside-binding soluble 3 binding protein (LGALS3BP), a secreted glycoprotein, are elevated in human cancers. Recently, we have identified LGALS3BP as a factor capable of stimulating angiogenesis of microvascular endothelial cells in vitro as well as in vivo. However, the potential therapeutic implications of LGALS3BP function blockade have not been explored yet. Here, we tested the ability of an anti-LGALS3BP mouse monoclonal antibody, SP-2, to antagonize LGALS3BP-induced angiogenesis and tumor growth. The antibody was found to inhibit endothelial cell tubulogenesis induced by either conditioned medium of breast cancer and melanoma cells or human recombinant LGALS3BP. In addition, SP-2 inhibited phosphorylation of FAK and its recruitment to membrane sites as well as AKT and ERK phosphorylation promoted by LGALS3BP. When used in vivo, the antibody restrained LGALS3BP-stimulated angiogenesis and growth of tumor xenografts. Furthermore, the combination of SP-2 and low-dose bevacizumab was more effective than either agent alone. Taken together, these results lead to consideration of SP-2 as a promising candidate for LGALS3BP-targeted therapy. Mol Cancer Ther; 13(4); 916–25. ©2014 AACR.
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- 2014
47. Long-Term Outcome of Neoadjuvant Endocrine Therapy with Aromatase Inhibitors in Elderly Women with Hormone Receptor-Positive Breast Cancer
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Pasquale Cioffi, Ettore Cianchetti, Marinella Zilli, Stefano Iacobelli, Giampiero Ausili Cefaro, Roberto Politi, Marta Di Nicola, Camilla Marinelli, Michele De Tursi, Paolo Noccioli, Antonino Grassadonia, Nicola Tinari, Simona Grossi, Domenico Angelucci, Laura Iezzi, Clara Natoli, and Saveria Tavoletta
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Oncology ,medicine.medical_specialty ,Time Factors ,Antineoplastic Agents, Hormonal ,Receptor, ErbB-2 ,medicine.medical_treatment ,Anastrozole ,Breast Neoplasms ,Breast Oncology ,Breast cancer ,Surgical oncology ,Internal medicine ,Nitriles ,medicine ,Humans ,Aromatase ,skin and connective tissue diseases ,Neoadjuvant therapy ,Aged ,Neoplasm Staging ,Retrospective Studies ,biology ,business.industry ,Aromatase Inhibitors ,Letrozole ,Carcinoma, Ductal, Breast ,Triazoles ,medicine.disease ,Prognosis ,Neoadjuvant Therapy ,Androstadienes ,Postmenopause ,Survival Rate ,Carcinoma, Lobular ,Tamoxifen ,Hormone receptor ,Chemotherapy, Adjuvant ,biology.protein ,Surgery ,Female ,Neoplasm Grading ,business ,medicine.drug ,Follow-Up Studies - Abstract
Background Aromatase inhibitors (AIs) are more effective than tamoxifen as neoadjuvant endocrine therapy (NET) for hormone receptor (HR)-positive breast cancer. Here we report the surgical and long-term outcome of elderly postmenopausal patients with locally advanced, HR-positive breast cancer treated with preoperative AIs. Methods Between January 2003 and December 2012, 144 postmenopausal patients inoperable with breast conservative surgery (BCS) received letrozole, anastrozole, or exemestane as NET. Patients underwent breast surgery and received adjuvant AIs. Adjuvant systemic therapy, chemotherapy and/or trastuzumab, and adjuvant radiotherapy were administered as appropriate, but limited to high-risk patients with few or no comorbidities. Results After a median follow-up of 49 months, 4 (3.0 %) patients had local relapse, 18 (12.5 %) had distant metastases, and 24 (17.0 %) died. BCS was performed in 121 (84.0 %) patients. A tumor size
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- 2014
48. Fulvestrant 500 milligrams as endocrine therapy for endocrine sensitive advanced breast cancer patients in the real world: the Ful500 prospective observational trial
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G. D'Auria, Clara Natoli, Maddalena Barba, A. Vaccaro, Enzo Maria Ruggeri, Patrizia Vici, Laura Iezzi, Luca Moscetti, Lucia Mentuccia, Maria Agnese Fabbri, M. Mauri, Antonino Grassadonia, Laura Pizzuti, Elena Iattoni, Carmine Roma, Isabella Sperduti, and Teresa Gamucci
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0301 basic medicine ,medicine.medical_specialty ,endocrine resistance ,03 medical and health sciences ,0302 clinical medicine ,Median follow-up ,Internal medicine ,medicine ,Clinical endpoint ,Endocrine system ,Progression-free survival ,Gynecology ,Fulvestrant ,fulvestrant ,business.industry ,endocrine therapy ,Cancer ,medicine.disease ,Metastatic breast cancer ,030104 developmental biology ,Oncology ,Tolerability ,030220 oncology & carcinogenesis ,metastatic breast cancer ,business ,medicine.drug ,Research Paper - Abstract
// Luca Moscetti 1, 8 , Maria Agnese Fabbri 1 , Clara Natoli 2 , Patrizia Vici 3 , Teresa Gamucci 4 , Isabella Sperduti 5 , Laura Iezzi 6 , Elena Iattoni 8 , Laura Pizzuti 3 , Carmine Roma 7 , Angela Vaccaro 4 , Giuliana D’Auria 1 , Mariella Mauri 7 , Lucia Mentuccia 4 , Antonino Grassadonia 2 , Maddalena Barba 3 and Enzo Maria Ruggeri 1 1 Division of Medical Oncology, AUSL Viterbo, Belcolle Hospital Strada Sammartinese, 01100 Viterbo, Italy 2 Department of Medical, Oral and Biotechnological Sciences and CeSI-MeT University G. D'Annunzio, Chieti-Pescara, 66100 Chieti, Italy 3 Division of Medical Oncology 2, Regina Elena National Cancer Institute, 00144 Roma, Italy 4 Medical Oncology Unit, ASL Frosinone, 03100 Frosinone, Italy 5 Biostatistics Unit, Istituto Regina Elena, 00144 Rome, Italy 6 Medical Oncology Unit, SS. Annunziata Hospital, 66100 Chieti, Italy 7 Division of Oncology, Azienda Ospedaliera San Giovanni Addolorata, 00184 Rome, Italy 8 Department of Oncology and Haematology, Azienda Ospedaliero Universitaria Policlinico di Modena, 41124 Modena, Italy Correspondence to: Luca Moscetti, email: moscetti.luca@policlinico.mo.it Keywords: fulvestrant, metastatic breast cancer, endocrine therapy, endocrine resistance Received: October 11, 2016 Accepted: March 04, 2017 Published: April 20, 2017 ABSTRACT The observational prospective trial herein presented aimed at evaluating the efficacy of fulvestrant 500 mg in the treatment of endocrine sensitive advanced breast cancer patients from the real world setting. The primary end point was clinical benefit rate (CBR). Secondary end points were overall survival (OS), progression free survival (PFS) and tolerability. One hundred sixty three patients were enrolled. At a median follow up of 20 months, the 61% of patients reached CBR, whose median duration was 10.8 months. Median PFS and OS were 7 and 35 months, respectively. Endocrine sensitive patients showed better PFS and OS. No relevant toxicity appeared when analyzing safety data. In multivariate analysis, visceral involvement, endocrine sensitivity and previous endocrine therapy were prognostic factor for PFS, whereas endocrine sensitivity and metastasis at diagnosis had prognostic relevance for OS. Estrogen receptor expression >50%, single metastatic site, and no prior endocrine therapy for advanced disease were predictive of CBR. In this prospective trial, fulvestrant 500 mg appeared to be a safe and active treatment and confirmed its efficacy in the daily clinical practice. A high percent expression of estrogen receptors (above 50%) was associated with higher CBR. Treatment was very well tolerated. Endocrine sensitivity had a major impact on treatment outcome. As expected, patients who had received first-line endocrine therapy for advanced disease exhibited worse outcome and a lower CBR.
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- 2016
49. Effectiveness of neoadjuvant trastuzumab and chemotherapy in HER2-overexpressing breast cancer
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Andrea Michelotti, Stefano Iacobelli, Giancarlo Bisagni, Patrizia Vici, Ilaria Ferrarini, Lucia Mentuccia, Corrado Ficorella, Isabella Sperduti, Stefania Gori, Riccardo Samaritani, Germano Zampa, Maria Mauri, Nicola Tinari, Michele Panebianco, Teresa Gamucci, Luca Moscetti, Clara Natoli, Laura Pizzuti, Michele De Tursi, and Antonino Grassadonia
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Oncology ,Cancer Research ,Survival ,Receptor, ErbB-2 ,medicine.medical_treatment ,Gene Expression ,Kaplan-Meier Estimate ,Breast cancer ,Trastuzumab ,Antineoplastic Combined Chemotherapy Protocols ,Anthracyclines ,skin and connective tissue diseases ,Neoadjuvant therapy ,Hematology ,Carcinoma, Ductal, Breast ,General Medicine ,Middle Aged ,Neoadjuvant Therapy ,Treatment Outcome ,Chemotherapy, Adjuvant ,Female ,Taxoids ,Neoadjuvant ,medicine.drug ,Adult ,medicine.medical_specialty ,Standard of care ,Neoplasms, Hormone-Dependent ,Locally advanced ,Breast Neoplasms ,Antibodies, Monoclonal, Humanized ,Disease-Free Survival ,Internal medicine ,HER2 ,medicine ,Humans ,neoplasms ,Aged ,Proportional Hazards Models ,Retrospective Studies ,Chemotherapy ,Original Paper ,Pathological complete response ,business.industry ,Retrospective cohort study ,medicine.disease ,Multivariate Analysis ,business - Abstract
Purpose Trastuzumab and chemotherapy is the current standard of care in HER2+ early or locally advanced breast cancer, but there are scanty literature data of its real world effectiveness. Methods We retrospectively reviewed 205 patients with HER2+ breast cancer diagnosed in 10 Italian Medical Oncology Units between July 2003 and October 2011. All patients received neoadjuvant systemic therapy (NST) with trastuzumab in association with chemotherapy. Many different chemotherapy regimens were used, even if 90 % of patients received schemes including anthracyclines and 99 % received taxanes. NST was administered for more than 21 weeks (median: 24) in 130/205 (63.4 %) patients, while trastuzumab was given for more than 12 weeks (median: 12 weeks) in 101/205 (49.3 %) patients. pCR/0 was defined as ypT0+ypN0, and pCR/is as ypT0/is+ypN0. Results pCR/0 was obtained in 24.8 % and pCR/is in 46.8 % of the patients. At multivariate logistic regression, nonluminal/HER2+ tumors (P
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- 2013
50. Long-term outcome of neoadjuvant systemic therapy for locally advanced breast cancer in routine clinical practice
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Lucia Anna Ursini, Stefano Iacobelli, Marinella Zilli, Pasquale Cioffi, Antonino Grassadonia, Domenico Angelucci, Michele De Tursi, Ettore Cianchetti, Laura Iezzi, Graziella Castrilli, Maria Teresa Scognamiglio, Nicola Tinari, Paolo Noccioli, Clara Natoli, Simona Grossi, and Giampiero Ausili-Cefaro
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Adult ,Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Retrospective ,Locally advanced ,Breast Neoplasms ,Prognostic factors ,Neoadjuvant chemotherapy ,Outcome (game theory) ,Systemic therapy ,Breast cancer ,Internal medicine ,Humans ,Medicine ,Combined Modality Therapy ,Routine clinical practice ,Neoadjuvant therapy ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Original Paper ,Pathological complete response ,business.industry ,Systemic chemotherapy ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,Neoadjuvant Therapy ,Treatment Outcome ,Female ,business - Abstract
Purpose The aim of this study is to evaluate the long-term outcome of patients with locally advanced breast cancer treated with neoadjuvant systemic chemotherapy (NST) in routine clinical practice. Methods Four hundred and nine patients were identified between January 1999 and December 2011. All patients received NST followed by surgery, adjuvant treatments and radiotherapy, as appropriate. Results At Kaplan–Meier analysis, patients with surgical stage III disease were more likely to develop distant metastasis and die from breast cancer (p
- Published
- 2012
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