Search

Your search keyword '"Paratore C"' showing total 3 results
Start Over Author "Paratore C" Topic brca1 protein
3 results on '"Paratore C"'

1. Germinal BRCA1-2 pathogenic variants (gBRCA1-2pv) and pancreatic cancer: epidemiology of an Italian patient cohort.

Author

Peretti U, Cavaliere A, Niger M, Tortora G, Di Marco MC, Rodriquenz MG, Centonze F, Rapposelli IG, Giordano G, De Vita F, Stuppia L, Avallone A, Ratti M, Paratore C, Forti LG, Orsi G, Valente MM, Gaule M, Macchini M, Carrera P, Calzavara S, Simbolo M, Melisi D, De Braud F, Salvatore L, De Lorenzo S, Chiarazzo C, Falconi M, Cascinu S, Milella M, and Reni M

Subjects
Adult, Aged, Aged, 80 and over, Female, Germ-Line Mutation, Humans, Italy epidemiology, Male, Middle Aged, Adenocarcinoma epidemiology, Adenocarcinoma genetics, BRCA1 Protein genetics, BRCA2 Protein genetics, Pancreatic Neoplasms epidemiology, Pancreatic Neoplasms genetics
Abstract

Objective: Germline BRCA1-2 pathogenic variants (gBRCApv) increase the risk of pancreatic cancer and predict for response to platinating agents and poly(ADP-ribose) polymerase inhibitors. Data on worldwide gBRCApv incidence among pancreatic ductal adenocarcinoma (PDAC) patients are sparse and describe a remarkable geographic heterogeneity. The aim of this study is to analyze the epidemiology of gBRCApv in Italian patients., Materials and Methods: Patients of any age with pancreatic adenocarcinoma, screened within 3 months from diagnosis for gBRCApv in Italian oncologic centers systematically performing tests without any selection. For the purposes of our analysis, breast, ovarian, pancreas, and prostate cancer in a patient's family history was considered as potentially BRCA-associated. Patients or disease characteristics were examined using the χ 2 test or Fisher's exact test for qualitative variables and the Student's t-test or Mann-Whitney test for continuous variables, as appropriate., Results: Between June 2015 and May 2020, 939 patients were tested by 14 Italian centers; 492 (52%) males, median age 62 years (range 28-87), 569 (61%) metastatic, 273 (29%) with a family history of potentially BRCA-associated cancers. gBRCA1-2pv were found in 76 patients (8.1%; 9.1% in metastatic; 6.4% in non-metastatic). The gBRCA2/gBRCA1 ratio was 5.4 : 1. Patients with gBRCApv were younger compared with wild-type (59 versus 62 years, P = 0.01). The gBRCApv rate was 17.1% among patients <40 years old, 10.4% among patients 41-50 years old, 9.2% among patients 51-60 years old, 6.7% among patients aged 61-70 years, and 6.2% among patients >70 years old (none out of 94 patients >73 years old). gBRCApv frequency in 845 patients <74 years old was 9%. Patients with/without a family history of potentially BRCA-associated tumors had 14%/6% mutations., Conclusion: Based on our findings of a gBRCApv incidence higher than expected in a real-life series of Italian patients with incident PDAC, we recommend screening all PDAC patients <74 years old, regardless of family history and stage, due to the therapeutic implications and cancer risk prevention in patients' relatives., Competing Interests: Disclosure MR reports travel expenses and personal honoraria for Advisory Boards from Celgene, Merck, Astra-Zeneca, Baxalta (2016), Baxter, Sanofi (2017), Servier, Shire, Eli Lilly, Pfizer (2016), Novocure (2016), and Novartis (2016), personal honoraria for steering committee work for AstraZeneca, and non-remunerated steering committee activities for Boston Pharmaceuticals. MF reports travel expenses and personal honoraria for Advisory Boards from Celgene, Novartis, Advanced Accelerators Applications, and Ipsen. SC reports travel expenses and personal honoraria for the following companies. Speaker: Amgen, Bayer, Eli Lilly, Servier. Advisory Boards: Amgen, Eli Lilly, Bayer, Baxter, Merck Sharp & Dohme (MSD), Servier. Consultant: Amgen, Baxter, Eli Lilly, Celgene, Novartis, MSD. Research grant: Celgene, Eisai. GT: Travel expenses and personal honoraria for Advisory Boards from Celgene, Merck, Astra-Zeneca, Servier. LS reports travel expenses and personal honoraria for Advisory Boards from Merck-Serono, Celgene, Roche, Sanofi, Servier, Bayer, Astra-Zeneca, Amgen. DM reports research grants and personal fees for consulting from Incyte Corporation; research grants and personal fees for consulting from Shire, Evotec, and iOnctura; research grants from Celgene, and personal fees for consulting from Eli Lilly and Baxter. FDV reports travel expenses and personal honoraria for Advisory Boards: Roche, Amgen, Celgene, Eli Lilly, Servier. MDM reports travel expenses and personal honoraria for Advisory Boards from Celgene. GG reports travel expenses and personal honoraria for Advisory Boards from Celgene (2016–2017–2018), Sanofi (2016–2018), Servier (2019). FDB reports personal honoraria for: Consultant Advisory Board: Ignyta, Bristol-Myers Squibb (BMS), Daiichi Sankyo, Pfizer, Octimet Oncology, Incyte, Teofarma, Pierre Fabre, Roche, EMD Serono, Sanofi, NMS Nerviano Medical Science, Pharm Research Associated (UK) Ltd; Speaker: BMS, Roche, MSD, Ignyta, Bayer, ACCMED, Dephaforum S.r.l., Nadirex, Merck, Biotechspert Ltd, PriME Oncology, Pfizer, Servier, Celgene, Tesaro, Loxo Oncology Inc., Sanofi, Healthcare Research & Pharmacoepidemiology. MN reports travel expenses from Celgene and personal honoraria for Advisory Board from EMD Serono. All the other authors have declared no conflicts of interest. Patient consent Before testing, all patients signed an informed consensus statement that was revised and approved by a local ethics committee and allowed, for genetic testing, and data collection, and analysis and elaboration. Data were irreversibly anonymized before entering into the database. Data availability statement Data are available upon reasonable request., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2021
Full Text
View/download PDF

2. Chemotherapy toxicity and activity in patients with pancreatic ductal adenocarcinoma and germline BRCA1-2 pathogenic variants (gBRCA1-2pv): a multicenter survey

Author

M. Scartozzi, Giampaolo Tortora, Giulia Orsi, Alessandro Cavaliere, Emiliano Tamburini, A.M. Militello, E. Penzo, L.G. Forti, Michele Milella, I. Bernardini, M. Macchini, Silvia Noventa, Michele Reni, M.M. Valente, Monica Niger, Stefano Cascinu, Andrea Spallanzani, K. Bencardino, M. Di Marco, Ingrid Garajová, A. Bittoni, U. Peretti, S. Mosconi, Silvia Bozzarelli, Maria Grazia Rodriquenz, C. Paratore, I.G. Rapposelli, Guido Giordano, S. De Lorenzo, Elisa Giommoni, Orsi, G., Di Marco, M., Cavaliere, A., Niger, M., Bozzarelli, S., Giordano, G., Noventa, S., Rapposelli, I. G., Garajova, I., Tortora, G., Rodriquenz, M. G., Bittoni, A., Penzo, E., De Lorenzo, S., Peretti, U., Paratore, C., Bernardini, I., Mosconi, S., Spallanzani, A., Macchini, M., Tamburini, E., Bencardino, K., Giommoni, E., Scartozzi, M., Forti, L., Valente, M. M., Militello, A. M., Cascinu, S., Milella, M., Reni, M., Orsi G., Di Marco M., Cavaliere A., Niger M., Bozzarelli S., Giordano G., Noventa S., Rapposelli I.G., Garajova I., Tortora G., Rodriquenz M.G., Bittoni A., Penzo E., De Lorenzo S., Peretti U., Paratore C., Bernardini I., Mosconi S., Spallanzani A., Macchini M., Tamburini E., Bencardino K., Giommoni E., Scartozzi M., Forti L., Valente M.M., Militello A.M., Cascinu S., Milella M., and Reni M.

Subjects
Cancer Research, medicine.medical_specialty, FOLFIRINOX, medicine.medical_treatment, pancreatic cancer, Gastroenterology, Germ Cell, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Original Research, chemotherapy toxicity, Cisplatin, Chemotherapy, Antineoplastic Combined Chemotherapy Protocol, business.industry, BRCA1 Protein, Carcinoma, Gemcitabine, Oxaliplatin, Irinotecan, Pancreatic Neoplasms, Germ Cells, Oncology, chemotherapy activity, Fluorouracil, Pancreatic Ductal, germline BRCA, chemotherapy dose intensity, Toxicity, business, medicine.drug, Human, Carcinoma, Pancreatic Ductal
Abstract

Background Germline BRCA1-2 pathogenic variants (gBRCA1-2pv)-related pancreatic ductal adenocarcinoma (PDAC) showed increased sensitivity to DNA cross-linking agents. This study aimed at exploring safety profile, dose intensity, and activity of different chemotherapy regimens in this setting. Patients and methods gBRCA1-2pv PDAC patients of any age and clinical tumor stage who completed a first course of chemotherapy were eligible. A descriptive analysis of chemotherapy toxicity, dose intensity, response, and survival outcomes was performed. Results A total of 85 gBRCA1-2pv PDAC patients treated in 21 Italian centers between December 2008 and March 2021were enrolled. Seventy-four patients were assessable for toxicity and dose intensity, 83 for outcome. Dose intensity was as follows: nab-paclitaxel 72%, gemcitabine 76% (AG); cisplatin 75%, nab-paclitaxel 73%, capecitabine 73%, and gemcitabine 65% (PAXG); fluorouracil 35%, irinotecan 58%, and oxaliplatin 64% (FOLFIRINOX). When compared with the literature, grade 3-4 neutropenia, thrombocytopenia, and diarrhea were increased with PAXG, and unmodified with AG and FOLFIRINOX. RECIST responses were numerically higher with the three- (81%) or four-drug (73%) platinum-containing regimens that outperformed AG (41%) and oxaliplatin-based doublets (56%). Carbohydrate antigen 19.9 (CA19.9) reduction >89% at nadir was reported in two-third of metastatic patients treated with triplets and quadruplets, as opposed to 33% and 45% of patients receiving oxaliplatin-based doublets or AG, respectively. All patients receiving AG experienced disease progression, with a median progression-free survival (mPFS) of 6.4 months, while patients treated with platinum-containing triplets or quadruplets had an mPFS >10.8 months. Albeit still immature, data on overall survival seemed to parallel those on PFS. Conclusions Our data, as opposed to figures expected from the literature, highlighted that platinum-based regimens provoked an increased toxicity on proliferating cells, when dose intensity was maintained, or an as-expected toxicity, when dose intensity was reduced, while no change in toxicity and dose intensity was evident with AG. Furthermore, an apparently improved outcome of platinum-based triplets or quadruplets over other regimens was observed., Highlights • Nab-paclitaxel plus gemcitabine dose intensity and toxicity were as expected from the literature. • Toxicity with platinum-based triplets was unmodified to the price of consistently reduced dose intensity. • Dose intensity for platinum-based quadruplets was preserved to the price of greater hematological toxicity and diarrhea. • RECIST and CA19.9 responses were higher with platinum-based triplets and quadruplets in metastatic patients. • Longer progression-free and overall survival were observed with platinum-based three- and four-drug regimens in stage IV (AJCC/UICC TNM 8th Edition, 2017) patients.

Published
2021

3. Germinal BRCA1-2 pathogenic variants (gBRCA1-2pv) and pancreatic cancer: epidemiology of an Italian patient cohort

Author

Michele Reni, M. Macchini, Maria Grazia Rodriquenz, F. Centonze, G. Tortora, I.G. Rapposelli, S. De Lorenzo, Michele Simbolo, Paola Carrera, A. Avallone, F. De Vita, S. Calzavara, C. Chiarazzo, Marina Gaule, Giulia Orsi, Alessandro Cavaliere, Margherita Ratti, L. Stuppia, M. Di Marco, C. Paratore, Michele Milella, F. de Braud, Monica Niger, Lisa Salvatore, Davide Melisi, Stefano Cascinu, L.G. Forti, G. Giordano, M.M. Valente, Massimo Falconi, U. Peretti, U. Peretti, A. Cavaliere, M. Niger, G. Tortora, M. C. Di Marco, M. G. Rodriquenz, F. Centonze, I. G. Rapposelli, G. Giordano, F. De Vita, L. Stuppia, A. Avallone, M. Ratti, C. Paratore, L. G. Forti, G. Orsi, M. M. Valente, M. Gaule, M. Macchini, P. Carrera, S. Calzavara, M. Simbolo, D. Melisi, F. De Braud, L. Salvatore, S. De Lorenzo, C. Chiarazzo, M. Falconi, S. Cascinu, M. Milella, M. Reni, Peretti, U, Cavaliere, A, Niger, M, Tortora, G, Di Marco, M C, Rodriquenz, M G, Centonze, F, Rapposelli, I G, Giordano, G, De Vita, F, Stuppia, L, Avallone, A, Ratti, M, Paratore, C, Forti, L G, Orsi, G, Valente, M M, Gaule, M, Macchini, M, Carrera, P, Calzavara, S, Simbolo, M, Melisi, D, De Braud, F, Salvatore, L, De Lorenzo, S, Chiarazzo, C, Falconi, M, Cascinu, S, Milella, M, Reni, M, Peretti, U., Cavaliere, A., Niger, M., Tortora, G., Di Marco, M. C., Rodriquenz, M. G., Centonze, F., Rapposelli, I. G., Giordano, G., De Vita, F., Stuppia, L., Avallone, A., Ratti, M., Paratore, C., Forti, L. G., Orsi, G., Valente, M. M., Gaule, M., Macchini, M., Carrera, P., Calzavara, S., Simbolo, M., Melisi, D., De Braud, F., Salvatore, L., De Lorenzo, S., Chiarazzo, C., Falconi, M., Cascinu, S., Milella, M., and Reni, M.

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Adenocarcinoma, familial cancer, Prostate cancer, Pancreatic cancer, Internal medicine, Epidemiology, Medicine, Humans, Family history, Germ-Line Mutation, Aged, Original Research, pancreatic cancer genetics, Aged, 80 and over, BRCA2 Protein, business.industry, BRCA1 Protein, Incidence (epidemiology), Middle Aged, pancreatic cancer genetic, medicine.disease, germline BRCA, epidemiology, pancreatic cancer genetics, familial cancer, Pancreatic Neoplasms, Exact test, Oncology, Italy, germline BRCA, Cohort, Female, epidemiology, business, Human
Abstract

Objective Germline BRCA1-2 pathogenic variants (gBRCApv) increase the risk of pancreatic cancer and predict for response to platinating agents and poly(ADP-ribose) polymerase inhibitors. Data on worldwide gBRCApv incidence among pancreatic ductal adenocarcinoma (PDAC) patients are sparse and describe a remarkable geographic heterogeneity. The aim of this study is to analyze the epidemiology of gBRCApv in Italian patients. Materials and methods Patients of any age with pancreatic adenocarcinoma, screened within 3 months from diagnosis for gBRCApv in Italian oncologic centers systematically performing tests without any selection. For the purposes of our analysis, breast, ovarian, pancreas, and prostate cancer in a patient's family history was considered as potentially BRCA-associated. Patients or disease characteristics were examined using the χ2 test or Fisher's exact test for qualitative variables and the Student's t-test or Mann–Whitney test for continuous variables, as appropriate. Results Between June 2015 and May 2020, 939 patients were tested by 14 Italian centers; 492 (52%) males, median age 62 years (range 28-87), 569 (61%) metastatic, 273 (29%) with a family history of potentially BRCA-associated cancers. gBRCA1-2pv were found in 76 patients (8.1%; 9.1% in metastatic; 6.4% in non-metastatic). The gBRCA2/gBRCA1 ratio was 5.4 : 1. Patients with gBRCApv were younger compared with wild-type (59 versus 62 years, P = 0.01). The gBRCApv rate was 17.1% among patients 70 years old (none out of 94 patients >73 years old). gBRCApv frequency in 845 patients, Highlights • This is the largest case series of incident PDAC patients screened for germline BRCA1-2 pathologic variants (gBRCApv). • The incidence of gBRCA1-2pv was 8.1% in the whole population; 9.1% in metastatic patients; 6.4% in non-metastatic patients. • No gBRCA1-2pv was observed over the age of 73. • These data suggest screening all PDAC patients

Published
2020

Catalog

Books, media, physical & digital resources
See catalog results