20 results on '"Barba, Maddalena"'
Search Results
2. Loss of HER2 and decreased T-DM1 efficacy in HER2 positive advanced breast cancer treated with dual HER2 blockade: the SePHER Study
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Bon, Giulia, Pizzuti, Laura, Laquintana, Valentina, Loria, Rossella, Porru, Manuela, Marchiò, Caterina, Krasniqi, Eriseld, Barba, Maddalena, 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, Barchiesi, Giacomo, Mazzotta, Marco, Marinelli, Daniele, Tomao, Silverio, Marchetti, Paolo, Valerio, Maria Rosaria, Mirabelli, Rosanna, Russo, Antonio, Fabbri, Maria Agnese, D’Ostilio, Nicola, Veltri, Enzo, Corsi, Domenico, Garrone, Ornella, Paris, Ida, Sarobba, Giuseppina, Giotta, Francesco, Garufi, Carlo, Cazzaniga, Marina, Del Medico, Pietro, Roselli, Mario, Sanguineti, Giuseppe, Sperduti, Isabella, Sapino, Anna, De Maria, Ruggero, Leonetti, Carlo, Di Leo, Angelo, Ciliberto, Gennaro, Falcioni, Rita, and Vici, Patrizia
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- 2020
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3. Breast cancer surgery during the Covid-19 pandemic: a monocentre experience from the Regina Elena National Cancer Institute of Rome
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Pelle, Fabio, Cappelli, Sonia, Graziano, Franco, Piarulli, Loredana, Cavicchi, Flavia, Magagnano, Domenico, De Luca, Assunta, De Vita, Roy, Pozzi, Marcello, Costantini, Maurizio, Varanese, Antonio, Panimolle, Massimo, Gullo, Pietro Paolo, Barba, Maddalena, Vici, Patrizia, Vizza, Enrico, Cognetti, Francesco, Sanguineti, Giuseppe, Saracca, Elena, Ciliberto, Gennaro, and Botti, Claudio
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- 2020
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4. Cancer patients and coronavirus disease 2019: evidence in context
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Barba, Maddalena, Krasniqi, Eriseld, Ciliberto, Gennaro, and Vici, Patrizia
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- 2020
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5. Coexisting YAP expression and TP53 missense mutations delineates a molecular scenario unexpectedly associated with better survival outcomes in advanced gastric cancer
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Pallocca, Matteo, Goeman, Frauke, De Nicola, Francesca, Melucci, Elisa, Sperati, Francesca, Terrenato, Irene, Pizzuti, Laura, Casini, Beatrice, Gallo, Enzo, Amoreo, Carla Azzurra, Vici, Patrizia, Di Lauro, Luigi, Buglioni, Simonetta, Diodoro, Maria Grazia, Pescarmona, Edoardo, Mazzotta, Marco, Barba, Maddalena, Fanciulli, Maurizio, De Maria, Ruggero, Ciliberto, Gennaro, and Maugeri-Saccà, Marcello
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- 2018
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6. Observational study of coagulation activation in early breast cancer: development of a prognostic model based on data from the real world setting
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Mandoj, Chiara, Pizzuti, Laura, Sergi, Domenico, Sperduti, Isabella, Mazzotta, Marco, Di Lauro, Luigi, Amodio, Antonella, Carpano, Silvia, Di Benedetto, Anna, Botti, Claudio, Ferranti, Francesca, Antenucci, Anna, D’Alessandro, Maria Gabriella, Marchetti, Paolo, Tomao, Silverio, Sanguineti, Giuseppe, Giordano, Antonio, Maugeri-Saccà, Marcello, Ciliberto, Gennaro, Conti, Laura, Vici, Patrizia, and Barba, Maddalena
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- 2018
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7. Body mass index modifies the relationship between γ-H2AX, a DNA damage biomarker, and pathological complete response in triple-negative breast cancer.
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Barba, Maddalena, Vici, Patrizia, Pizzuti, Laura, Lauro, Luigi Di, Sergi, Domenico, Benedetto, Anna Di, Ercolani, Cristiana, Sperati, Francesca, Terrenato, Irene, Botti, Claudio, Mentuccia, Lucia, Iezzi, Laura, Gamucci, Teresa, Natoli, Clara, Vitale, Ilio, Mottolese, Marcella, Maria, Ruggero De, Maugeri-Saccà, Marcello, Di Lauro, Luigi, and Di Benedetto, Anna
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BODY mass index , *DNA damage , *TRIPLE-negative breast cancer , *OBESITY , *CANCER cells ,BREAST cancer chemotherapy - Abstract
Background: Body mass index (BMI) is largely investigated as a prognostic and predictive factor in triple-negative breast cancer (TNBC). Overweight and obesity are linked to a variety of pathways regulating tumor-promoting functions, including the DNA damage response (DDR). The DDR physiologically safeguards genome integrity but, in a neoplastic background, it is aberrantly engaged and protects cancer cells from chemotherapy. We herein verified the role of BMI on a previously assessed association between DDR biomarkers and pathological complete response (pCR) in TNBC patients treated with neoadjuvant chemotherapy (NACT).Methods: In this retrospective analysis 54 TNBC patients treated with NACT were included. The relationship between DDR biomarkers, namely phosphorylated H2A Histone Family Member X (γ-H2AX) and phosphorylated checkpoint kinase 1 (pChk1), and pCR was reconsidered in light of BMI data. The Pearson's Chi-squared test of independence (2-tailed) and the Fisher Exact test were employed to assess the relationship between clinical-molecular variables and pCR. Uni- and multivariate logistic regression models were used to identify variables impacting pCR. Internal validation was carried out.Results: We observed a significant association between elevated levels of the two DDR biomarkers and pCR in patients with BMI < 25 (p = 0.009 and p = 0.022 for γ-H2AX and pChk1, respectively), but not in their heavier counterpart. Results regarding γ-H2AX were confirmed in uni- and multivariate models and, again, for leaner patients only (γ-H2AXhigh vs γ-H2AXlow: OR 10.83, 95% CI: 1.79-65.55, p = 0.009). The consistency of this finding was confirmed upon internal validation.Conclusions: The predictive significance of γ-H2AX varies according to BMI status. Indeed, elevated levels of γ-H2AX seemed associated with lower pCR rate only in leaner patients, whereas differences in pCR rate according to γ-H2AX levels were not appreciable in heavier patients. Larger investigations are warranted concerning the potential role of BMI as effect modifier of the relationship between DDR-related biomarkers and clinical outcomes in TNBC. [ABSTRACT FROM AUTHOR]- Published
- 2017
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8. Topographic expression of the Hippo transducers TAZ and YAP in triple-negative breast cancer treated with neoadjuvant chemotherapy.
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Vici, Patrizia, Ercolani, Cristiana, Di Benedetto, Anna, Pizzuti, Laura, Di Lauro, Luigi, Sperati, Francesca, Terrenato, Irene, Gamucci, Teresa, Natoli, Clara, Di Filippo, Franco, Botti, Claudio, Barba, Maddalena, Mottolese, Marcella, De Maria, Ruggero, and Maugeri-Saccà, Marcello
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TRIPLE-negative breast cancer ,ADJUVANT treatment of cancer ,CANCER chemotherapy ,HEALTH outcome assessment ,GENE expression - Abstract
Background: The Hippo signaling acts as a tumor-suppressor pathway that negatively regulates TAZ and YAP. Increasing evidence supports the activation of TAZ and YAP in breast cancer. Moreover, the Hippo pathway is involved in the biology of non-neoplastic cells residing in the tumor microenvironment. On this basis, we herein assessed TAZ and YAP in triple-negative breast cancer and its surrounding microenvironemnt in order to investigate their impact on pathological complete response (pCR) and tumor recurrence. Methods: Sixty-one triple-negative breast cancer patients treated with neoadjuvant chemotherapy were retrospectively evaluated. TAZ and YAP were assessed by immunohistochemistry and classified as positive or negative according to the percentage of tumor-expressing cells, cellular localization, and staining intensity. TAZ and YAP expression was also evaluated in non-lymphocytic stromal cells, tumor-infiltrating lymphocytes (TILs) and endothelial cells. The Pearson's Chi-squared test of independence was used to test the association between TAZ/YAP and clinical-molecular factors. A multivariate logistic regression model was generated to identify variables impacting pCR. The Kaplan-Meier method and the log-rank test were used for estimating and comparing survival curves. Cox proportional regression models were built to evaluate the risk of recurrence for the variables considered. Internal validation was carried out with a re-sampling without replacement method. Results: We did not observe any impact on pCR rate when TAZ and YAP were addressed singularly. Conversely, the combined expression of YAP in tumor cells and non-lymphocytic stromal cells was an independent predictor of reduced pCR rate in the multivariate model (OR 7.13, 95% CI: 1.23-41.41, p = 0.029). Next, the combined expression of TAZ and YAP was associated with shorter disease-free survival (DFS) in multivariate analysis (HR 3.07, 95% CI: 1.24-7.61, p= 0.016). The robustness of these findings were internally validated. Conclusions: The combined expression of YAP in TNBC cells and in the surrounding stroma seems to be associated with a decreased likelihood to achieve pCR. Conversely, the combined expression of TAZ and YAP in tumor cells conferred poor survival outcomes. [ABSTRACT FROM AUTHOR]
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- 2016
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9. Role of gonadotropin-releasing hormone analogues in metastatic male breast cancer: results from a pooled analysis.
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Di Lauro, Luigi, Pizzuti, Laura, Barba, Maddalena, Sergi, Domenico, Sperduti, Isabella, Mottolese, Marcella, Amoreo, Carla Azzurra, Belli, Franca, Vici, Patrizia, Speirs, Valerie, Santini, Daniele, De Maria, Ruggero, and Maugeri-Saccà, Marcello
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BREAST cancer research ,GONADOTROPIN releasing hormone ,AROMATASE inhibitors ,CANCER in men ,CANCER treatment - Abstract
Background: Male breast cancer is a rare malignancy. Despite the lack of prospectively generated data from trials in either the adjuvant or metastatic setting, patients are commonly treated with hormone therapies. Much controversy exists over the use of gonadotropin-releasing hormone analogues in metastatic male breast cancer patients. We conducted this study to provide more concrete ground on the use of gonadotropin-releasing hormone analogues in this setting. Methods: We herein present results from a pooled analysis including 60 metastatic male breast cancer patients treated with either an aromatase inhibitor or cyproterone acetate as a monotherapy (23 patients) or combined with a gonadotropin-releasing hormone analogue (37 patients). Results: Overall response rate was 43.5 % in patients treated with monotherapy and 51.3 % with combination therapy (p = 0.6). Survival outcomes favored combination therapy in terms of median progression-free survival (11.6 months versus 6 months; p = 0.05), 1-year progression-free survival rate (43.2 % versus 21.7 %; p = 0.05), median overall survival (29.7 months versus 22 months; p = 0.05), and 2-year survival rate (64.9 % versus 43.5 %; p =0.05). Conclusions: In metastatic male breast cancer patients, the combined use of gonadotropin-releasing hormone analogues and aromatase inhibitors or antiandrogens seems to be associated with greater efficacy, particularly in terms of survival outcomes, compared with monotherapy. Collectively, these results encourage considering these agents in the metastatic setting. [ABSTRACT FROM AUTHOR]
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- 2015
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10. Efficacy of chemotherapy in metastatic male breast cancer patients: a retrospective study.
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Di Lauro, Luigi, Pizzuti, Laura, Barba, Maddalena, Sergi, Domenico, Sperduti, Isabella, Mottolese, Marcella, Del Medico, Pietro, Belli, Franca, Vici, Patrizia, De Maria, Ruggero, and Maugeri-Saccà, Marcello
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CANCER chemotherapy ,METASTASIS ,BREAST cancer treatment ,COMBINATION drug therapy ,HORMONE therapy ,ANTHRACYCLINES - Abstract
Background: The role of chemotherapy in the treatment of metastatic male breast cancer patients remains unknown, and the only available evidence stem from small, retrospective series evaluating outdated drugs and/or regimens. Methods: In this retrospective study we evaluated the activity of polychemotherapy, consisting of three-drug (anthracycline-containing and anthracycline-free) regimens, as a first-line therapy for metastatic male breast cancer patients who had received at least one prior endocrine therapy. Results: Fifty patients treated between 1978 and 2013 were included in the present analysis. Regarding best response, we recorded 1 (2%) complete response and 27 (54%) partial responses, for an overall response rate of 56% (95% CI, 42.2-69.8). Considering stable disease, the disease control rate was 84%. Median progression-free survival was 7.2 months (95% CI, 5.9-8.5), and median overall survival was 14.2 months (95% CI, 12.2-16.2). Albeit we observed some differences for all the outcomes explored when comparing anthracycline-containing and anthracycline-free regimens, they were not statistically significant. Conclusions: Chemotherapy, consisting in both anthracycline-containing and anthracycline-free regimens, showed encouraging antitumor activity in metastatic male breast cancer patients previously treated with endocrine therapy. [ABSTRACT FROM AUTHOR]
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- 2015
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11. FOLFIRI as a second-line therapy in patients with docetaxel-pretreated gastric cancer: a historical cohort.
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Maugeri-Saccà, Marcello, Pizzuti, Laura, Sergi, Domenico, Barba, Maddalena, Belli, Franca, Fattoruso, Silvia Ileana, Giannarelli, Diana, Amodio, Antonella, Boggia, Sara, Vici, Patrizia, and Di Lauro, Luigi
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DOCETAXEL ,FLUOROURACIL ,CLINICAL trials ,CANCER patients ,ANTINEOPLASTIC agents ,CANCER treatment - Abstract
Background: The role of second-line therapy in gastric cancer patients mostly stemmed from clinical trials with monochemotherapy carried out in Asian countries. Nevertheless, these results cannot be broadly generalized as molecular studies suggested the existence of different sets of deregulated gene networks correlated with ethnicity. In the present study, we investigated the activity and safety of FOLFIRI given as a second-line therapy in metastatic gastric or gastro-esophageal junction cancer patients who experienced disease progression on or after first-line docetaxel-containing chemotherapy. Methods: Patients with histologically confirmed metastatic gastric cancer who failed docetaxel-containing first-line therapy and who received FOLFIRI in second line were eligible for the study. Seventy patients treated at three Italian cancer centers between 2005 and 2012 entered the study. Patients received every 2 weeks irinotecan 180 mg/m2 as 1 h infusion on day 1, folinic acid 100 mg/m2 intravenously days 1-2, and fluorouracil as a 400 mg/m
2 bolus and then 600 mg/m2 continuous infusion over 22 hours days 1-2. Results: We observed 1(1.4%) complete response, 15 (21.4%) partial response, for an overall response rate of 22.8% (95% confidence interval (CI): 13.4-32.3). Stable disease was recorded in 21 (30%) patients. Median progression-free survival and overall survival were 3.8 months (95% CI: 3.3-4.4) and 6.2 months (95% CI: 5.3-7.1), respectively. The treatment was well tolerated, as the most common G3-4 toxicities were neutropenia (28.5%) and diarrhea (14.5%). Conclusions: FOLFIRI appears an effective and safe treatment option for pretreated metastatic gastric cancer patients, and deserves further investigation in randomized clinical trials. [ABSTRACT FROM AUTHOR]- Published
- 2013
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12. Gemcitabine-oxaliplatin (GEMOX) as salvage treatment in pretreated epithelial ovarian cancer patients.
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Vici, Patrizia, Sergi, Domenico, Pizzuti, Laura, Mariani, Luciano, Arena, Maria Grazia, Barba, Maddalena, Maugeri-Saccà, Marcello, Vincenzoni, Cristina, Vizza, Enrico, Corrado, Giacomo, Paoletti, Giancarlo, Tomao, Federica, Tomao, Silverio, Giannarelli, Diana, and Di Lauro, Luigi
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OXALIPLATIN ,OVARIAN cancer patients ,OVARIAN cancer treatment ,NEUTROPENIA ,FEBRILE neutropenia ,THERAPEUTICS - Abstract
Background: Currently, no clearly superior management strategy exists for recurrent, platinum-resistant ovarian cancer. We tested the efficacy and safety of gemcitabine combined with oxaliplatin (GEMOX) in a multicentre phase II clinical trial. Methods: Forty one patients with recurrent, platinum-resistant ovarian cancer were enrolled. Prior to study entry, all the participants had received at least one platinum-based regimen. Gemcitabine was administered at 1000 mg/m2 as protracted infusion (100 min) on day 1, and oxaliplatin at the dose of 100 mg/m2 on day 2 in a 2 hour infusion. Cycles were repeated every two weeks. Results: We observed an overall response rate of 37% [95% Confidence Interval (CI), 22.3-51.7]. Objective responses plus disease stabilization (clinical benefit) occurred in 78% of patients. Median progression-free survival was 6.8 months (95% CI, 5.8-7.8), and median overall survival was 16.5 months (95% CI, 12.2-20.8). Median time to self-reported symptom relief, which was described by 22 out of 27 symptomatic patients (81.5%), was 4 weeks (range, 2-8). Grade 4 neutropenia and febrile neutropenia were observed in 2 (5%) and 1 (2.5%) patients, while grade 3 anemia was encountered in 2 (5%) patients, respectively. The most common adverse effects of any grade were gastrointestinal symptoms, fatigue and neutropenia. Nine patients (22%) experienced mild allergic reaction to oxaliplatin, with no treatment discontinuation. Conclusions: In our cohort of recurrent, platinum-resistant ovarian cancer patients, GEMOX showed encouraging activity and manageable toxicity. Under circumstances requiring a rapid disease control, this combination regimen may offer a particularly viable option, particularly in heavily pretreated patients. [ABSTRACT FROM AUTHOR]
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- 2013
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13. Molecular profiles of screen detected vs. symptomatic breast cancer and their impact on survival: results from a clinical series.
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Crispo, Anna, Barba, Maddalena, D'Aiuto, Giuseppe, De Laurentiis, Michelino, Grimaldi, Maria, Rinaldo, Massimo, Caolo, Giuseppina, D'Aiuto, Massimiliano, Capasso, Immacolata, Esposito, Emanuela, Amore, Alfonso, Di Bonito, Maurizio, Botti, Gerardo, and Montella, Maurizio
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MOLECULAR biology , *MEDICAL screening , *BREAST cancer diagnosis , *CLINICAL medicine , *DISEASES in women , *HEALTH outcome assessment - Abstract
Background: Stage shift is widely considered a major determinant of the survival benefit conferred by breast cancer screening. However, factors and mechanisms underlying such a prognostic advantage need further clarification. We sought to compare the molecular characteristics of screen detected vs. symptomatic breast cancers and assess whether differences in tumour biology might translate into survival benefit. Methods: In a clinical series of 448 women with operable breast cancer, the Kaplan-Meier method and the log-rank test were used to estimate the likelihood of cancer recurrence and death. The Cox proportional hazard model was used for the multivariate analyses including mode of detection, age at diagnosis, tumour size, and lymph node status. These same models were applied to subgroups defined by molecular subtypes. Results: Screen detected breast cancers tended to show more favourable clinicopathological features and survival outcomes compared to symptomatic cancers. The luminal A subtype was more common in women with mammography detected tumours than in symptomatic patients (68.5 vs. 59.0%, p=0.04). Data analysis across categories of molecular subtypes revealed significantly longer disease free and overall survival for screen detected cancers with a luminal A subtype only (p=0.01 and 0.02, respectively). For women with a luminal A subtype, the independent prognostic role of mode of detection on recurrence was confirmed in Cox proportional hazard models (p=0.03). An independent role of modality of detection on survival was also suggested (p=0.05). Conclusions: Molecular subtypes did not substantially explain the differences in survival outcomes between screened and symptomatic patients. However, our results suggest that molecular profiles might play a role in interpreting such differences at least partially. Further studies are warranted to reinterpret the efficacy of screening programmes in the light of tumour biology. [ABSTRACT FROM AUTHOR]
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- 2013
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14. The burden of breast cancer in Italy: mastectomies and quadrantectomies performed between 2001 and 2008 based on nationwide hospital discharge records.
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Piscitelli, Prisco, Barba, Maddalena, Crespi, Massimo, Di Maio, Massimo, Santoriello, Antonio, D¿Aiuto, Massiliamo, Fucito, Alfredo, Losco, Arturo, Pentimalli, Francesca, Maranta, Pasquale, Chitano, Giovanna, Argentiero, Alberto, Neglia, Cosimo, Distante, Alessandro, luca Di Tanna, Gian, Brandi, Maria Luisa, Mazza, Alfredo, Marino, Ignazio R., and Giordano, Antonio
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Background: Where population coverage is limited, the exclusive use of Cancer Registries might limit ascertainment of incident cancer cases. We explored the potentials of Nationwide hospital discharge records (NHDRs) to capture incident breast cancer cases in Italy. Methods: We analyzed NHDRs for mastectomies and quadrantectomies performed between 2001 and 2008. The average annual percentage change (AAPC) and related 95% Confidence Interval (CI) in the actual number of mastectomies and quadrantectomies performed during the study period were computed for the full sample and for subgroups defined by age, surgical procedure, macro-area and singular Region. Re-admissions of the same patients were separately presented. Results: The overall number of mastectomies decreased, with an AAPC of -2.1% (-2.3 -1.8). This result was largely driven by the values observed for women in the 45 to 64 and 65 to 74 age subgroups (-3.0%, -3.4 -3.6 and -3.3%, -3.8 -2.8, respectively). We observed no significant reduction in mastectomies for women in the remaining age groups. Quadrantectomies showed an overall +4.7 AAPC (95%CI:4.5-4.9), with no substantial differences by age. Analyses by geographical area showed a remarkable decrease in mastectomies, with inter-regional discrepancies ossibly depending upon variability in mammography screening coverage and adherence. Quadrantectomies significantly increased, with Southern Regions presenting the highest average rates. Data on repeat admissions within a year revealed a total number of 46,610 major breast surgeries between 2001 and 2008, with an overall +3.2% AAPC (95%CI:2.8-3.6). Conclusions: In Italy, NHDRs might represent a valuable supplemental data source to integrate Cancer Registries in cancer surveillance. [ABSTRACT FROM AUTHOR]
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- 2012
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15. An instrument to assess quality of life in relation to nutrition: item generation, item reduction and initial validation.
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Schünemann, Holger J., Sperati, Francesca, Barba, Maddalena, Santesso, Nancy, Melegari, Camilla, Akl, Elie A., Guyatt, Gordon, and Muti, Paola
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QUALITY of life ,NUTRITION ,HEALTH ,HUMAN ecology ,QUESTIONNAIRES - Abstract
Background: It is arguable that modification of diet, given its potential for positive health outcomes, should be widely advocated and adopted. However, food intake, as a basic human need, and its modification may be accompanied by sensations of both pleasure and despondency and may consequently affect to quality of life (QoL). Thus, the feasibility and success of dietary changes will depend, at least partly, on whether potential negative influences on QoL can be avoided. This is of particular importance in the context of dietary intervention studies and in the development of new food products to improve health and well being. Instruments to measure the impact of nutrition on quality of life in the general population, however, are few and far between. Therefore, the aim of this project was to develop an instrument for measuring QoL related to nutrition in the general population. Methods and results: We recruited participants from the general population and followed standard methodology for quality of life instrument development (identification of population, item selection, n = 24; item reduction, n = 81; item presentation, n = 12; pretesting of questionnaire and initial validation, n = 2576; construct validation n = 128; and test-retest reliability n = 20). Of 187 initial items, 29 were selected for final presentation. Factor analysis revealed an instrument with 5 domains. The instrument demonstrated good cross-sectional divergent and convergent construct validity when correlated with scores of the 8 domains of the SF-36 (ranging from -0.078 to 0.562, 19 out of 40 tested correlations were statistically significant and 24 correlations were predicted correctly) and good test-retest reliability (intra-class correlation coefficients from 0.71 for symptoms to 0.90). Conclusions: We developed and validated an instrument with 29 items across 5 domains to assess quality of life related to nutrition and other aspects of food intake. The instrument demonstrated good face and construct validity as well as good reliability. Future work will focus on the evaluation of longitudinal construct validity and responsiveness. [ABSTRACT FROM AUTHOR]
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- 2010
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16. Lifetime total and beverage specific - alcohol intake and prostate cancer risk: a case-control study.
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Barba, Maddalena, McCann, Susan E., Schünemann, Holger J., Stranges, Saverio, Fuhrman, Barbara, De Placido, Sabino, Carruba, Giuseppe, Freudenheim, Jo L., Trevisan, Maurizio, Russell, Marcia, Nochajski, Tom, and Muti, Paola
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ALCOHOL drinking , *PROSTATE cancer , *CANCER risk factors , *NUTRITION - Abstract
Background: We investigated lifetime alcohol consumption and prostate cancer risk in a casecontrol study conducted in Buffalo, NY (1998-2001). Methods: The study included 88 men, aged 45 to 85 years with incident, histologically-confirmed prostate cancer and 272 controls. We conducted extensive in-person interviews regarding lifetime alcohol consumption and other epidemiologic data. Results: Prostate cancer risk was not associated with lifetime intake of total and beverage specific ethanol. In addition we found no association with number of drinks per day (average drinks per day over the lifetime) or drinks per drinking day (average drinks per day on drinking days only over the lifetime). However, we observed an inverse association with the total number of drinking years. Men in the lowest tertile of total drinking years had a two-fold prostate cancer risk than men in the highest tertile (OR 2.16, 95% CI 0.98-4.78, p for trend <0.05). Conclusion: Our results suggest that alcohol intake distribution across lifetime may play a more important role in prostate cancer etiology than total lifetime consumption. [ABSTRACT FROM AUTHOR]
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- 2004
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17. Expression of the Hippo transducer TAZ in association with WNT pathway mutations impacts survival outcomes in advanced gastric cancer patients treated with first-line chemotherapy.
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Melucci, Elisa, Casini, Beatrice, Ronchetti, Livia, Pizzuti, Laura, Sperati, Francesca, Pallocca, Matteo, De Nicola, Francesca, Goeman, Frauke, Gallo, Enzo, Amoreo, Carla Azzurra, Sergi, Domenico, Terrenato, Irene, Vici, Patrizia, Di Lauro, Luigi, Diodoro, Maria Grazia, Pescarmona, Edoardo, Barba, Maddalena, Mazzotta, Marco, Mottolese, Marcella, and Fanciulli, Maurizio
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BIOMEDICAL transducers ,CANCER treatment ,CANCER chemotherapy ,ADENOCARCINOMA ,HEALTH outcome assessment - Abstract
Background: An extensive crosstalk co-regulates the Hippo and Wnt pathway. Preclinical studies revealed that the Hippo transducers YAP/TAZ mediate a number of oncogenic functions in gastric cancer (GC). Moreover, comprehensive characterization of GC demonstrated that the Wnt pathway is targeted by oncogenic mutations. On this ground, we hypothesized that YAP/TAZ- and Wnt-related biomarkers may predict clinical outcomes in GC patients treated with chemotherapy.Methods: In the present study, we included 86 patients with advanced GC treated with first-line chemotherapy in prospective phase II trials or in routine clinical practice. Tissue samples were immunostained to evaluate the expression of YAP/TAZ. Mutational status of key Wnt pathway genes (CTNNB1, APC and FBXW7) was assessed by targeted DNA next-generation sequencing (NGS). Survival curves were estimated and compared by the Kaplan-Meier product-limit method and the log-rank test, respectively. Variables potentially affecting progression-free survival (PFS) were verified in univariate Cox proportional hazard models. The final multivariate Cox models were obtained with variables testing significant at the univariate analysis, and by adjusting for all plausible predictors of the outcome of interest (PFS).Results: We observed a significant association between TAZ expression and Wnt mutations (Chi-squared p = 0.008). Combined TAZ expression and Wnt mutations (TAZpos/WNTmut) was more frequently observed in patients with the shortest progression-free survival (negative outliers) (Fisher p = 0.021). Uni-and multivariate Cox regression analyses revealed that patients whose tumors harbored the TAZpos/WNTmut signature had an increased risk of disease progression (univariate Cox: HR 2.27, 95% CI 1.27-4.05, p = 0.006; multivariate Cox: HR 2.73, 95% CI 1.41-5.29, p = 0.003). Finally, the TAZpos/WNTmut signature negatively impacted overall survival.Conclusions: Collectively, our findings indicate that the oncogenic YAP/TAZ-Wnt crosstalk may be active in GC, conferring chemoresistant traits that translate into adverse survival outcomes. [ABSTRACT FROM AUTHOR]- Published
- 2018
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18. Urinary estrogen metabolites and prostate cancer: a case-control study and meta-analysis.
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Barba M, Yang L, Schünemann HJ, Sperati F, Grioni S, Stranges S, Westerlind KC, Blandino G, Gallucci M, Lauria R, Malorni L, and Muti P
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- Aged, Case-Control Studies, Chromatography, Liquid, Estrogens metabolism, Humans, Male, Mass Spectrometry, Middle Aged, Risk Factors, Estrogens urine, Hydroxyestrones urine, Prostatic Neoplasms urine
- Abstract
Objective: To investigate prostate cancer (Pca) risk in relation to estrogen metabolism, expressed as urinary 2-hydroxyestrone (2-OHE1), 16alpha-hydroxyestrone (16alpha-OHE1) and 2-OHE1 to 16alpha-OHE1 ratio., Methods: We conducted a case-control study within the Western New York Health Cohort Study (WNYHCS) from 1996 to 2001. From January 2003 through September 2004, we completed the re-call and follow-up of 1092 cohort participants. Cases (n = 26) and controls (n = 110) were matched on age, race and recruitment period according to a 1:4 ratio. We used the unconditional logistic regression to compute crude and adjusted odds ratios (OR) and 95% confident interval (CI) of Pca in relation to 2-OHE1, 16alphaOHE1 and 2-OHE1 to 16alpha-OHE1 by tertiles of urine concentrations (stored in a biorepository for an average of 4 years). We identified age, race, education and body mass index as covariates. We also conducted a systematic review of the literature which revealed no additional studies, but we pooled the results from this study with those from a previously conducted case-control study using the DerSimonian-Laird random effects method., Results: We observed a non-significant risk reduction in the highest tertile of 2-OHE1 (OR 0.72, 95% CI 0.25-2.10). Conversely, the odds in the highest tertile of 16alpha-OHE1 showed a non-significant risk increase (OR 1.76 95% CI 0.62-4.98). There was a suggestion of reduced Pca risk for men in the highest tertile of 2-OHE1 to 16alpha-OHE1 ratio (OR 0.56, 95% CI 0.19-1.68). The pooled estimates confirmed the association between an increased Pca risk and higher urinary levels of 16alpha-OHE1 (third vs. first tertile: OR 1.82, 95% CI 1.09-3.05) and the protective effect of a higher 2-OHE 1 to 16alpha-OHE1 ratio (third vs. first tertile: OR 0.53, 95% CI 0.31-0.90)., Conclusion: Our study and the pooled results provide evidence for a differential role of the estrogen hydroxylation pathway in Pca development and encourage further study.
- Published
- 2009
- Full Text
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19. Low-molecular-weight heparins are superior to vitamin K antagonists for the long term treatment of venous thromboembolism in patients with cancer: a cochrane systematic review.
- Author
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Akl EA, Barba M, Rohilla S, Terrenato I, Sperati F, Muti P, and Schünemann HJ
- Subjects
- Humans, Neoplasms drug therapy, Randomized Controlled Trials as Topic, Venous Thromboembolism etiology, Anticoagulants therapeutic use, Heparin, Low-Molecular-Weight therapeutic use, Neoplasms complications, Venous Thromboembolism drug therapy, Vitamin K antagonists & inhibitors
- Abstract
Background: Cancer and its therapies increase the risk of venous thromboembolism. Compared to patients without cancer, patients with cancer anticoagulated for venous thromboembolism are more likely to develop recurrent thrombotic events and major bleeding. Addressing all important outcomes including harm is of great importance to make evidence based health care decisions. The objective of this study was to compare low molecular weight heparin (LMWH) and oral anticoagulants (vitamin K antagonist (VKA) and ximelagatran) for the long term treatment of venous thromboembolism in patients with cancer., Methods: A systematic review of the medical literature. We followed the Cochrane Collaboration methodology for conducting systematic reviews. We assessed methodological quality for each outcome by grading the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology., Results: Eight randomized controlled trials (RCTs) were eligible and reported data for patients with cancer. The quality of evidence was low for death and moderate for recurrent venous thromboembolism. LMWH, compared to VKA provided no statistically significant survival benefit (Hazard ratio (HR) = 0.96; 95% CI 0.81 to 1.14) but a statistically significant reduction in venous thromboembolism (HR = 0.47; 95% (Confidence Interval (CI) = 0.32 to 0.71). There was no statistically significant difference between LMWH and VKA in bleeding outcomes (RR = 0.91; 95% CI = 0.64 to 1.31) or thrombocytopenia (RR = 1.02; 95% CI = 0.60 to 1.74)., Conclusion: For the long term treatment of venous thromboembolism in patients with cancer, LMWH compared to VKA reduces venous thromboembolism but not death.
- Published
- 2008
- Full Text
- View/download PDF
20. Parenteral anticoagulation may prolong the survival of patients with limited small cell lung cancer: a Cochrane systematic review.
- Author
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Akl EA, van Doormaal FF, Barba M, Kamath G, Kim SY, Kuipers S, Middeldorp S, Yosuico V, Dickinson HO, and Schünemann HJ
- Subjects
- Anticoagulants administration & dosage, Anticoagulants adverse effects, Carcinoma, Small Cell etiology, Carcinoma, Small Cell mortality, Fondaparinux, Heparin, Low-Molecular-Weight administration & dosage, Heparin, Low-Molecular-Weight adverse effects, Heparin, Low-Molecular-Weight therapeutic use, Humans, Lung Neoplasms etiology, Polysaccharides administration & dosage, Polysaccharides adverse effects, Polysaccharides therapeutic use, Survival Analysis, Treatment Outcome, Anticoagulants therapeutic use, Carcinoma, Small Cell drug therapy, Lung Neoplasms drug therapy
- Abstract
Background: To determine the efficacy and safety of heparin (unfractionated heparin (UFH) or low-molecular-weight-heparin (LMWH)) and fondaparinux in improving the survival of patients with cancer., Methods: We conducted in January 2007 a comprehensive search for relevant randomized clinical trials (RCTs). We used a standardized form to extract in duplicate data on methodological quality, participants, interventions and outcomes of interest including all cause mortality, thromboembolic events, and bleeding events. We assessed the methodological quality for each outcome by grading the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, Results: Of 3986 identified citations, we included 5 RCTs, none of which evaluated fondaparinux. The quality of evidence was moderate for survival, low for major and minor bleeding, and very low for DVT. Heparin therapy was associated with a statistically and clinically significant survival benefit (hazard ratio (HR) = 0.77; 95%CI = 0.65-0.91). In subgroup analyses, patients with limited small cell lung cancer experienced a clear survival benefit (HR = 0.56; 95%CI = 0.38-0.83). The survival benefit was not statistically significant for either patients with extensive small cell lung cancer (HR = 0.80; 95%CI = 0.60-1.06) or patients with advanced cancer (HR = 0.84; 95%CI = 0.68-1.03). The increased risk of bleeding with heparin was not statistically significant (relative risk (RR) = 1.78; 95%CI = 0.73-4.38)., Conclusion: This review suggests a survival benefit of heparin in cancer patients in general, and in patients with limited small cell lung cancer in particular.
- Published
- 2008
- Full Text
- View/download PDF
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