61 results on '"M. Libertini"'
Search Results
2. The Network Profile Summary: exploring network science through the lens of student motivation.
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Ralucca Gera, Jessica M. Libertini, Jonathan W. Roginski, and Anthony Zupancic
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- 2018
- Full Text
- View/download PDF
3. Supplementary Figure 2 from Dacarbazine in Solitary Fibrous Tumor: A Case Series Analysis and Preclinical Evidence vis-à-vis Temozolomide and Antiangiogenics
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P.G. Casali, N. Zaffaroni, S. Pilotti, A. Gronchi, T. Negri, D. Cominetti, E. Palassini, M. Libertini, A. Messina, C. Morosi, E. Tamborini, F. Bozzi, M. Tortoreto, and S. Stacchiotti
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PDF file, 227K, SFT xenotransplanted in SCID mice pathologic evaluation before and after treatment. A and B Pre-treatment samples: high-grade sarcoma aspects mixed with cartilaginous (A) and osseous component (B). C and D Post-sunitinib, post-bevacizumab and post-pazopanib samples. 120 days after the end of treatment with sunitinib (C), bevacizumab (D) xenografts were sacrificed. The tumor samples were all made of hypercellular viable, mainly spindle tumor cells, intermingled with osteoid matrix. Pazopanib (E) xenograft was instead sacrificed soon after treatment end, Even in this case tumor sample appeared to be completely vital.
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- 2023
4. Data from Dacarbazine in Solitary Fibrous Tumor: A Case Series Analysis and Preclinical Evidence vis-à-vis Temozolomide and Antiangiogenics
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P.G. Casali, N. Zaffaroni, S. Pilotti, A. Gronchi, T. Negri, D. Cominetti, E. Palassini, M. Libertini, A. Messina, C. Morosi, E. Tamborini, F. Bozzi, M. Tortoreto, and S. Stacchiotti
- Abstract
Purpose: To explore the value of triazines in solitary fibrous tumor (SFT).Experimental Design: We retrospectively reviewed 8 cases of patients with SFT treated with dacarbazine (1,200 mg/m2 every 3 weeks) as from January 2012. Then, we studied a dedifferentiated-SFT subcutaneously xenotransplanted into severe combined immunodeficient (SCID) mice. Dacarbazine, temozolomide, sunitinib, bevacizumab, and pazopanib were administered at their reported optimal doses for the mouse model when mean tumor volume (TV) was about 80 mm3; each experimental groups included 6 mice. Drug activity was assessed as tumor volume inhibition percentage (TVI%). Dacarbazine was tested according to two different schedules of administration. One hunded twenty days after treatment interruption, mouse tumor samples were analyzed.Results: Among the eight patients treated with dacarbazine, best response evaluation criteria in solid tumors responses (RECIST) were three partial responses, 4 stable disease, 1 progression. Two responsive patients had paraneoplastic hypoglycemia that disappeared after 10 days from starting dacarbazine. In the dedifferentiated-SFT xenograft model, dacarbazine and temozolomide showed the highest antitumor activity (about 95% TVI), confirmed pathologically. Sunitinib and pazopanib were only marginally active (52% and 41% TVI, respectively), whereas bevacizumab caused a 78% TVI. No tumor regrowth was observed up to 100 days from end of treatment with temozolomide and dacarbazine, whereas secondary progression followed sunitinib, pazopanib, and bevacizumab interruption.Conclusions: Dacarbazine as single agent has antitumor activity in SFT. Our preclinical results suggest a cytotoxic effect of temozolomide and dacarbazine, as compared with a cytostatic role for sunitinib, pazopanib, and bevacizumab. A phase II study on dacarbazine in advanced SFT is planned. Clin Cancer Res; 19(18); 5192–201. ©2013 AACR.
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- 2023
5. Supplementary Figure 1 from Dacarbazine in Solitary Fibrous Tumor: A Case Series Analysis and Preclinical Evidence vis-à-vis Temozolomide and Antiangiogenics
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P.G. Casali, N. Zaffaroni, S. Pilotti, A. Gronchi, T. Negri, D. Cominetti, E. Palassini, M. Libertini, A. Messina, C. Morosi, E. Tamborini, F. Bozzi, M. Tortoreto, and S. Stacchiotti
- Abstract
PDF file, 256K, A Human primary tumor: morphology (i.e., patternless growth, collagen deposition, moderate cellularity, mitotic index (>4X10 High Power Field (HPF), as shown in panel 1) and immunophenotype (i.e., diffuse positivity for CD34, as shown in panel 1/a) were consistent with a malignant SFT. Immunohistochemistry was positive for PDGFRB expression (panel 1/b). B Human relapsed tumor: morphology was consistent with a dedifferentiated SFT (DSFT), being marked by the abrupt transition from areas with MSFT aspects similar to what observed in the primary tumor (panel 2) to areas with high-grade sarcoma features (panel 3). High-grade areas showed hypercellularity (panel 3/a), chondroid (panel 3/b) and osteoid differentiation (panel 3/c). C Xenograft tumor: morphology was consistent with a high-grade DSFT (panel 4), superimposable to what observed in panel B, 3a/3b/3c, again with presence of mineralized trabeculaes and osteoid (panel 4/a). Immunohistochemistry was positive for PDGFRB expression (panel 4/b). Phospho receptor tyrosine kinase (pRTK) array (ARY001 Proteome ProfilerTM Array, R&D Systems) showed similar profiles for human relapsed tumor (panel B, 3/d) and xenograft (panel C, 4/c) with the activation of PDGFRA (green boxes), PDGFRB (red boxes) and VEGFR1 (yellow boxes). White boxes are the proteome profiler negative controls.
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- 2023
6. Supplementary Figure 3 from Dacarbazine in Solitary Fibrous Tumor: A Case Series Analysis and Preclinical Evidence vis-à-vis Temozolomide and Antiangiogenics
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P.G. Casali, N. Zaffaroni, S. Pilotti, A. Gronchi, T. Negri, D. Cominetti, E. Palassini, M. Libertini, A. Messina, C. Morosi, E. Tamborini, F. Bozzi, M. Tortoreto, and S. Stacchiotti
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PDF file, 110K, The xenografts were sacrificed five days after starting sunitinib, bevacizumab and pazopanib. One sample was obtained also 4 weeks after the end of treatment with pazopanib. PDGFRB and VEGFR2 activation was analyzed trough immunoprecipitation (IP) and western blotting (WB). PDGFRB activation was reduced by sunitinib and pazopanib, while VEGFR2 activation was decreased by bevacizumab and pazopanib. A re-activation of both PDGFRB and VEGFR2 was detected after 4 weeks of treatment with pazopanib.
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- 2023
7. Comparing Gradient Descent with Automatic Differentiation and Particle Swarm Optimization Techniques for Estimating Tumor Blood Flow Parameters in Contrast-Enhanced Imaging
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Steven Seay, Jessica M. Libertini, and Kao-Pu Chang
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Numerical Analysis ,Automatic differentiation ,Applied Mathematics ,General Engineering ,Particle swarm optimization ,Blood flow ,01 natural sciences ,Theoretical Computer Science ,010101 applied mathematics ,Computational Mathematics ,Computational Theory and Mathematics ,Collocation method ,TRACER ,Medical imaging ,Leverage (statistics) ,0101 mathematics ,Gradient descent ,Biological system ,Software ,Mathematics - Abstract
In this preliminary report, two optimization approaches, gradient descent with automatic differentiation and particle swarm optimization, are presented, applied, and compared in an effort to leverage dynamic information collected during contrast-enhanced medical imaging of tumors to estimate four blood flow parameters: perfusion, permeability surface area product, volume of the plasma, and volume of the interstitial space. Using Fick’s law on a simple two-compartment model, the resulting PDEs are numerically integrated using a collocation method for a set of boundary and initial conditions and known values of the parameters, and the resulting tracer concentrations were spatially integrated to generate truth data of signal intensity as a function of time only. After using physical constraints on the boundaries to recover reasonable estimates for two of the parameters, the two optimization approaches are used in an attempt to recover estimates for the remaining two parameters. The resulting efficacy and efficiency of the two optimization approaches are compared.
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- 2019
8. Promoting Interdisciplinary and Mathematical Modelling Through Competitions
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Sergey Kushnarev and Jessica M. Libertini
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Value (ethics) ,Competition (economics) ,Knowledge management ,business.industry ,ComputingMilieux_COMPUTERSANDEDUCATION ,Sociology ,business ,Complex problems ,Social relation - Abstract
As we aim to prepare students to tackle increasingly complex problems in the real world, we believe that extracurricular contests can provide a fun, low-stakes environment to practice mathematical and interdisciplinary modelling skills. In this chapter, we discuss the value of providing such experiences for students and provide an overview of a popular international competition. We then describe rural and urban variations of a local modelling competition designed to provide instant feedback and foster social interaction among student modelers. After offering some thoughts on developing appropriate problems for these competitions, we close by sharing some informal feedback from students and faculty who have participated in these competitions.
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- 2020
9. 318O Clinical portrait of the SARS-CoV-2 epidemic in European cancer patients
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D.J. Pinato, A. Zambelli, A. Bertuzzi, A. Marrari, N. Saoudi-Gonzalez, O. Mirallas, M. Galazi, D. Generali, S. Grisanti, C. Tondini, A. Prat, J. Tabernero, R. Mesia, R. Salazar, A. Sureda, M. Franchi, L. Chiudinelli, D.G. Illescas, M. Libertini, and A. Gennari
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0301 basic medicine ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Hematology ,Article - Published
- 2020
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- View/download PDF
10. From CENTRAL to SENTRAL (SErum aNgiogenesis cenTRAL): Circulating Predictive Biomarkers to Anti-VEGFR Therapy
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Vittorina Zagonel, Maria Giulia Zampino, Carla Codecà, Pina Ziranu, Nicoletta Pella, Gerardo Rosati, M. Libertini, Domenico Germano, Bruno Daniele, Pietro Sozzi, Luigi Cavanna, Mariaelena Casagrande, Antonio Zizzi, Roberto Labianca, Alberto Zaniboni, Sara Lonardi, Mario Scartozzi, Stefano Cascinu, Riccardo Giampieri, Eleonora Lai, Marco Puzzoni, Daris Ferrari, Laura Demurtas, Valeria Pusceddu, Giampieri, R., Ziranu, P., Daniele, B., Zizzi, A., Ferrari, D., Lonardi, S., Zaniboni, A., Cavanna, L., Rosati, G., Casagrande, M., Pella, N., Demurtas, L., Zampino, M. G., Sozzi, P., Pusceddu, V., Germano, D., Lai, E., Zagonel, V., Codeca, C., Libertini, M., Puzzoni, M., Labianca, R., Cascinu, S., and Scartozzi, M.
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0301 basic medicine ,Oncology ,Placental growth factor ,Cancer Research ,medicine.medical_specialty ,Bevacizumab ,Circulating biomarkers ,Colorectal cancer ,FGF2 ,bevacizumab ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,Folinic acid ,angiogenesis ,0302 clinical medicine ,Internal medicine ,medicine ,Progression-free survival ,business.industry ,circulating biomarkers ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,VEGF ,Colon cancer ,Irinotecan ,Regimen ,030104 developmental biology ,colon cancer ,PlGF ,030220 oncology & carcinogenesis ,FOLFIRI ,Angiogenesis ,business ,medicine.drug - Abstract
Background: In the last decade, a series of analyses failed to identify predictive biomarkers of resistance/susceptibility for anti-angiogenic drugs in metastatic colorectal cancer (mCRC). We conducted an exploratory preplanned analysis of serum pro-angiogenic factors (SErum aNgiogenesis-cenTRAL) in 72 mCRC patients enrolled in the phase II CENTRAL (ColorEctalavastiNTRiAlLdh) trial, with the aim to identify potential predictive factors for sensitivity/resistance to first line folinic acid-fluorouracil-irinotecan regimen (FOLFIRI) plus bevacizumab. Methods: First-line FOLFIRI/bevacizumab patients were prospectively assessed for the following circulating pro-angiogenic factors, evaluated with ELISA (enzyme-linked immunosorbent assay)-based technique at baseline and at every cycle: Vascular endothelial growth factor A (VEGF-A), hepatocyte growth factor (HGF), stromal derived factor-1 (SDF-1), placental derived growth factor (PlGF), fibroblast growth factor-2 (FGF-2), monocyte chemotactic protein-3 (MCP-3), interleukin-8 (IL-8). Results: Changes in circulating FGF-2 levels among different blood samples seemed to correlate with clinical outcome. Patients who experienced an increase in FGF-2 levels at the second cycle of chemotherapy compared to baseline, had a median Progression Free Survival (mPFS) of 12.85 vs. 7.57 months (Hazard Ratio&mdash, HR: 0.73, 95% Confidence Interval&mdash, CI: 0.43-1.27, p = 0.23). Similar results were seen when comparing FGF-2 concentrations between baseline and eight-week time point (mPFS 12.98 vs. 8.00 months, HR: 0.78, 95% CI: 0.46&ndash, 1.33, p = 0.35). Conclusions: Our pre-planned, prospective analysis suggests that circulating FGF-2 levels&rsquo, early increase could be used as a marker to identify patients who are more likely to gain benefit from FOLFIRI/bevacizumab first-line therapy.
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- 2020
11. Comparing demographics of signatories to public letters on diversity in the mathematical sciences
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Jude Higdon, Brian Katz, Chad M. Topaz, Christian Michael Smith, James Cart, Anelise Hanson Shrout, Carrie Diaz Eaton, Jessica M. Libertini, Drew Lewis, and Kenan Ince
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Male ,Ethnic group ,Social Sciences ,Graduates ,Cultural Anthropology ,050602 political science & public administration ,Ethnicities ,SocArXiv|Social and Behavioral Sciences|Science and Technology Studies ,Minority Groups ,media_common ,bepress|Social and Behavioral Sciences|Other Social and Behavioral Sciences ,Multidisciplinary ,Statistics ,05 social sciences ,Gender studies ,Cultural Diversity ,0506 political science ,Physical Sciences ,Medicine ,Educational Status ,Crowdsourcing ,Female ,Privilege (social inequality) ,Research Article ,Societies, Scientific ,Computer and Information Sciences ,050101 languages & linguistics ,Universities ,Science ,media_common.quotation_subject ,History and Overview (math.HO) ,Ethnic Groups ,Mistake ,Power (social and political) ,Social Justice ,FOS: Mathematics ,SocArXiv|Social and Behavioral Sciences|Other Social and Behavioral Sciences ,Humans ,0501 psychology and cognitive sciences ,bepress|Social and Behavioral Sciences|Science and Technology Studies ,Personnel Selection ,Demography ,White (horse) ,Mathematical sciences ,business.industry ,Mathematics - History and Overview ,Contingency Tables ,Achievement ,United States ,Anthropology ,People and Places ,bepress|Social and Behavioral Sciences ,Population Groupings ,SocArXiv|Social and Behavioral Sciences ,business ,Undergraduates ,Mathematics ,Diversity (politics) - Abstract
In its December 2019 edition, the \textit{Notices of the American Mathematical Society} published an essay critical of the use of diversity statements in academic hiring. The publication of this essay prompted many responses, including three public letters circulated within the mathematical sciences community. Each letter was signed by hundreds of people and was published online, also by the American Mathematical Society. We report on a study of the signatories' demographics, which we infer using a crowdsourcing approach. Letter A highlights diversity and social justice. The pool of signatories contains relatively more individuals inferred to be women and/or members of underrepresented ethnic groups. Moreover, this pool is diverse with respect to the levels of professional security and types of academic institutions represented. Letter B does not comment on diversity, but rather, asks for discussion and debate. This letter was signed by a strong majority of individuals inferred to be white men in professionally secure positions at highly research intensive universities. Letter C speaks out specifically against diversity statements, calling them "a mistake," and claiming that their usage during early stages of faculty hiring "diminishes mathematical achievement." Individuals who signed both Letters B and C, that is, signatories who both privilege debate and oppose diversity statements, are overwhelmingly inferred to be tenured white men at highly research intensive universities. Our empirical results are consistent with theories of power drawn from the social sciences., 21 pages, 2 tables, 2 figures; minor textual edits made to previous version
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- 2019
12. Improving Applied Mathematics Education
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Ron Buckmire, Jessica M. Libertini, Ron Buckmire, and Jessica M. Libertini
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- Mathematics--Study and teaching
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This book presents various contemporary topics in applied mathematics education and addresses both interested undergraduate instructors and STEM education researchers. The diverse set of topics of this edited volume range from analyzing the demographics of the United States mathematics community, discussing the teaching of calculus using modern tools, engaging students to use applied mathematics to learn about and solve problems of global significance, developing a general education course for humanities and social sciences students that features applications of mathematics, and describing local mathematical modeling competitions and their use in providing authentic experiences for students in applying mathematics to real world situations. The authors represent diversity along multiple dimensions of difference: race, gender, institutional affiliation, and professional experience.
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- 2021
13. First-line FOLFIRI and bevacizumab in patients with advanced colorectal cancer prospectively stratified according to serum LDH: final results of the GISCAD (Italian Group for the Study of Digestive Tract Cancers) CENTRAL (ColorEctalavastiNTRiAlLdh) trial
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Vittorina Zagonel, Carla Codecà, Gerardo Rosati, Maria Giulia Zampino, Mario Scartozzi, Stefano Cascinu, Domenico Germano, Sara Lonardi, Bruno Daniele, Nicoletta Pella, Pietro Sozzi, Luigi Cavanna, M. Libertini, Riccardo Giampieri, Roberto Labianca, Alberto Zaniboni, Daris Ferrari, Marco Puzzoni, Giampieri, Riccardo, Puzzoni, Marco, Daniele, Bruno, Ferrari, Dari, Lonardi, Sara, Zaniboni, Alberto, Cavanna, Luigi, Rosati, Gerardo, Pella, Nicoletta, Zampino, Maria Giulia, Sozzi, Pietro, Germano, Domenico, Zagonel, Vittorina, Codecà, Carla, Libertini, Michela, Labianca, Roberto, Cascinu, Stefano, and Scartozzi, Mario
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0301 basic medicine ,Male ,Cancer Research ,predictive factors ,Colorectal cancer ,Leucovorin ,Angiogenesis Inhibitors ,Colorectal Neoplasm ,Gastroenterology ,predictive factor ,Basal (phylogenetics) ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,Clinical endpoint ,80 and over ,Prospective Studies ,Prospective cohort study ,bevacizumab ,colorectal cancer ,LDH ,Adult ,Aged ,Aged, 80 and over ,Bevacizumab ,Camptothecin ,Colorectal Neoplasms ,Disease-Free Survival ,Female ,Fluorouracil ,Humans ,L-Lactate Dehydrogenase ,Middle Aged ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,FOLFIRI ,medicine.drug ,Angiogenesis Inhibitor ,Human ,medicine.medical_specialty ,03 medical and health sciences ,Internal medicine ,medicine ,Antineoplastic Combined Chemotherapy Protocol ,business.industry ,medicine.disease ,Surgery ,Clinical trial ,Prospective Studie ,030104 developmental biology ,Clinical Study ,business - Abstract
Background: Previous findings suggested that bevacizumab might be able to improve response rate (RR) in colorectal cancer patients with high lactic dehydrogenase (LDH) basal levels. Methods: We conducted a phase II trial to prospectively ascertain whether bevacizumab in combination with FOLFIRI could have an improved clinical activity in patients with high LDH serum levels. Primary end point of the study was RR; secondary end points were median overall survival and median progression-free survival (mPFS). Results: A total of 81 patients were enrolled. No difference in terms of ORR (39% vs 31% for low vs high LDH level stratum, P=0.78) and mPFS (14.16 vs 10.29 months, HR: 1.07, 95% CI: 0.51–2.24, P=0.83) between the strata was observed, whereas overall survival (OS) was significantly longer for patients with low LDH (24.85 vs 15.14 months, HR: 4.08, 95% CI: 1.14–14.61, P=0.0004). In a not-pre-planned exploratory analysis using different cut-off ranges for LDH, we observed RR up to 70%, with no improvement in progression-free survival or OS. Conclusions: The CENTRAL trial failed to demonstrate that high LDH levels were related to a significantly improved RR in patients receiving first-line FOLFIRI and bevacizumab. The LDH serum levels should then no further be investigated as a predictive factor in this setting.
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- 2017
14. The Network Profile Summary: exploring network science through the lens of student motivation
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Ralucca Gera, Jessica M. Libertini, Anthony Zupancic, Jonathan W. Roginski, Naval Postgraduate School (U.S.), and Applied Mathematics and Center for Cyber Warfare
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Control and Optimization ,Computer Networks and Communications ,Computer science ,Pedagogy ,Applied Mathematics ,05 social sciences ,Complex networks ,050301 education ,Network science ,02 engineering and technology ,Assessment ,Management Science and Operations Research ,MUSIC ,Through-the-lens metering ,Computational Mathematics ,Human–computer interaction ,020204 information systems ,ComputingMilieux_COMPUTERSANDEDUCATION ,0202 electrical engineering, electronic engineering, information engineering ,0503 education - Abstract
The article of record as published may be found at http://dx.doi.org/10.1093/comnet/cnx040 Productive learning environments strike a balance between student motivation and the necessary learning outcomes associated with a particular course. This article explores one way to achieve such a balance and discusses some of the subtle benefits that spring from that balance. We designed a network science course that achieves course objectives and at the same time allows students to develop, test, and monitor a network of their own choosing. Rather than use canned networks, we introduce a set of assignments called the Network Profile Summary in which students continually apply newly learned course concepts to their selected networks and are therefore able to realize the utility and place of these concepts. This course design fosters student motivation and encourages independent learning. Under this pedagogical paradigm, students began to see coursework, concepts and feedback as productive and globally meaningful rather than corrective and locally meaningful. U.S. Department of Defense
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- 2017
15. Impact of age and gender on the safety and efficacy of chemotherapy plus bevacizumab in metastatic colorectal cancer: a pooled analysis of TRIBE and TRIBE2 studies
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Gemma Zucchelli, Emanuela Dell'Aquila, Beatrice Borelli, Federica Urbano, Giacomo Allegrini, Tiziana Latiano, Federica Marmorino, Alfredo Falcone, Gianluca Masi, Francesca Bergamo, Daniele Rossini, Monica Ronzoni, Sara Lonardi, Stefano Cordio, Angela Buonadonna, Giovanni Randon, M. Libertini, Margherita Ratti, Luigi Boni, Alessandro Passardi, Roberto Moretto, Vincenzo Ricci, Alessandra Boccaccino, G. Aprile, Emiliano Tamburini, Chiara Cremolini, and Nicoletta Pella
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0301 basic medicine ,age ,FOLFOXIRI/bevacizumab ,gender ,metastatic colorectal cancer ,Age Factors ,Aged ,Aged, 80 and over ,Antineoplastic Combined Chemotherapy Protocols ,Bevacizumab ,Camptothecin ,Colorectal Neoplasms ,Female ,Fluorouracil ,Humans ,Kaplan-Meier Estimate ,Leucovorin ,Male ,Middle Aged ,Nausea ,Neoplasm Metastasis ,Organoplatinum Compounds ,Progression-Free Survival ,Sex Characteristics ,Treatment Outcome ,Vomiting ,Colorectal cancer ,0302 clinical medicine ,FOLFOX ,80 and over ,FOLFOXIRI ,Hematology ,Chemotherapy regimen ,Oncology ,030220 oncology & carcinogenesis ,FOLFIRI ,medicine.symptom ,medicine.drug ,medicine.medical_specialty ,03 medical and health sciences ,Internal medicine ,medicine ,business.industry ,medicine.disease ,030104 developmental biology ,business ,Febrile neutropenia - Abstract
BACKGROUND The phase III TRIBE and TRIBE2 studies randomized metastatic colorectal cancer patients to first-line FOLFOXIRI/bevacizumab or a doublet (FOLFIRI or FOLFOX)/bevacizumab. The studies demonstrated a significant benefit from the triplet at the price of an increased incidence of chemotherapy-related adverse events (AEs). In both trials, males and females aged between 18 and 70 years with ECOG PS ≤2 and between 71 and 75 years with ECOG PS = 0 were eligible. We investigated the effect of FOLFOXIRI/bevacizumab versus doublets/bevacizumab according to age and gender. PATIENTS AND METHODS Subgroup analyses according to age (
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- 2019
16. 447P Long term survival with regorafenib: REALITY (real life in Italy) trial - A GISCAD Study
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Alessandra Boccaccino, Marco Puzzoni, C. Cremolini, Maria Banzi, Manuela Dettori, Veronica Conca, A. Zaniboni, Francesca Bergamo, Mario Scartozzi, Floriana Nappo, Eleonora Lai, G. Piacentini, Giuseppe Luigi Banna, F. Andreozzi, A. Cavo, M. Libertini, Saverio Cinieri, Francesco Iachetta, Gemma Zucchelli, and Silvia Rota
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medicine.medical_specialty ,chemistry.chemical_compound ,Oncology ,chemistry ,business.industry ,Regorafenib ,Long term survival ,medicine ,Hematology ,Intensive care medicine ,business - Published
- 2020
17. Prognostic and predictive role of body mass index (BMI) in metastatic colorectal cancer (mCRC): A pooled analisys of TRIBE and TRIBE-2 studies by GONO
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Lorenzo Marcucci, Alessandra Boccaccino, Daniele Santini, G. Aprile, Francesca Bergamo, Daniele Rossini, Rossana Intini, L. Fanchini, Angela Buonadonna, Monica Ronzoni, Gianluca Masi, Federica Morano, Evaristo Maiello, A. Falcone, Federica Marmorino, Stefano Cordio, M. Libertini, E. Fea, Emanuela Dell'Aquila, Marco Stellato, Dell'Aquila, Emanuela, Rossini, Daniele, Galletti, Alessandro, Stellato, Marco, Boccaccino, Alessandra, Conca, Veronica, Germani, Marco Maria, Bergamo, Francesca, Daniel, Francesca, Spagnoletti, Andrea, Provenzano, Leonardo, Tomasello, Gianluca, Zaniboni, Alberto, Buonadonna, Angela, Fanchini, Laura, Cupini, Samanta, Carlomagno, Chiara, Caponnetto, Salvatore, Rapisardi, Stefania, and Santini, Daniele
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medicine.medical_specialty ,Organoplatinum Compounds ,Bevacizumab ,bevacizumab folfoxiri ,Colorectal cancer ,Population ,Leucovorin ,bevacizumab doublet ,Body mass index ,metastatic colorectal cancer ,prognostic and predictive factor ,TRIBE ,TRIBE 2 ,FOLFOX ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Obesity ,Body mass index, bevacizumab folfoxiri, bevacizumab doublet, metastatic colorectal cancer, prognostic and predictive factor, TRIBE, TRIBE 2 ,education ,education.field_of_study ,FOLFOXIRI ,Rectal Neoplasms ,business.industry ,Gastroenterology ,Hematology ,Prognosis ,medicine.disease ,Treatment Outcome ,Oncology ,Colonic Neoplasms ,FOLFIRI ,Camptothecin ,Fluorouracil ,Underweight ,medicine.symptom ,Colorectal Neoplasms ,business ,medicine.drug - Abstract
Background Obesity is associated with an increased risk of development and recurrence of colorectal cancer. The role of obesity in mCRC patients (pts) is still unclear, especially in those treated with triplet plus bevacizumab (bev). The aim of our study was to evaluate the prognostic and predictive role of BMI in mCRC pts treated with FOLFOXIRI plus bev or FOLFIRI/FOLFOX plus bev in the TRIBE and TRIBE-2 trial. Methods 1160 pts enrolled in TRIBE and TRIBE-2 trials were included. Baseline height and weight were used to assign patients to one of the following BMI categories: underweight (group A = BMI 30 kg/m2; 156 pts). Results In our population, no differences in terms of PFS (p = 0.38) or OS (p = 0.93) resulted between three groups. No interaction effect between treatment arm and BMI was evident in terms of PFS (HR: 0.70 [95%CI: 0.40-1.22]; HR: 0.78 [95%CI: 0.68-0.89]; HR: 0.66 [95%CI: 0.48-0.91]; p for interaction= 0.61, in group A,B,C respectively) or OS (Group A HR: 0.62 [95%CI: 0.31-1.25]; Group B HR: 0.84 [95%CI: 0.72-0.98];Group C HR: 0.67 [95%CI: 0.46-0.99] p for interaction= 0.44). No statistically significant difference in terms of dose reductions due to toxicities were required according to BMI in overall population (p = 0.48) and in pts treated with FOLFOXIRI plus bev (p = 0.57). Conclusions BMI was not prognostic either for PFS or for OS in our population. Our analyses showed that the advantage of FOLFOXIRI plus bev versus FOLFIRI/FOLFOX plus bev was independent from BMI. Legal entity responsible for the study Daniele Santini. Funding Has not received any funding. Disclosure A. Falcone: Advisory / Consultancy, advisory board and Institutional funding to research: Amgen; Advisory / Consultancy, advisory board and Institutional funding to research: Roche; Advisory / Consultancy, advisory board and Institutional funding to research: Bayer; Advisory / Consultancy, advisory board and Institutional funding to research: Merck; Advisory / Consultancy, advisory board and Institutional funding to research: Servier; Advisory / Consultancy, advisory board and Institutional funding to research: Lilly. All other authors have declared no conflicts of interest.
- Published
- 2019
18. Tactile Learning Activities in Mathematics
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Julie Barnes, Jessica M. Libertini, Julie Barnes, and Jessica M. Libertini
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- Touch, Mathematical recreations, Mathematics--Study and teaching (Higher)--Activity programs, Teaching--Methodology, Educational innovations
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Q: What do feather boas, cookies, and paper shredders have in common? A: They are all ingredients that have the potential to help your undergraduate students understand a variety of mathematical concepts. In this book, 43 faculty from a wide range of institutional settings share a total of 64 hands-on activities that allow students to physically engage with mathematical ideas ranging from the basics of precalculus to special topics appropriate for upper-level courses. Each learning activity is presented in an easy-to-read recipe format that includes a list of supplies; a narrative briefly describing the reasons, logistics, and helpful hints for running the activity; and a page that can be used as a handout in class. Purchase of the book also includes access to electronic printable versions of the handouts. With so many activities, it might be hard to decide where to start. For that reason, there are four indices to help the reader navigate this book: a concept index, a course index, an author index, and a main ingredient index. In addition to providing activities for precalculus, calculus, commonly required mathematics courses for majors, and more specialized upper-level electives, there is also a section describing how to modify many of the activities to fit into a liberal arts mathematics class. Whether you are new to using hands-on activities in class or are more experienced, the authors hope that this book will encourage and inspire you to explore the possibilities of using more hands-on activities in your classes. Bon appétit!
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- 2018
19. Using Applications to Motivate the Learning of Differential Equations
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Jessica M. Libertini and Karen M. Bliss
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Value (ethics) ,Differential equation ,Computer science ,Human–computer interaction ,ComputingMilieux_COMPUTERSANDEDUCATION ,Field (computer science) ,Variety (cybernetics) - Abstract
The field of differential equations is rich with applications that can be used to motivate and facilitate learning. This paper presents a variety of ways a modeling-focus can be adopted, based on the desired learning outcomes of an individual course. We offer an overview of the implementation of this approach within a specific course and identify several modeling scenarios that can be used either to introduce and motivate a lesson topic or to allow students to apply recently acquired skills to a meaningful problem. While using applications has clear benefits for our students, many of whom go on to pursue engineering degrees, adding these components to a course can be challenging, so this paper also addresses some logistical approaches to folding these applications into a course with success. Student feedback is also provided as evidence of the value of adopting such an approach.
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- 2016
20. The role of adjuvant therapy in resectable SBA: A different clinicians attitude with a relevant impact on outcome
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Francesca Bergamo, M.L. Riggi, Vittorina Zagonel, Letizia Procaccio, Marco Puzzoni, Stefano Cascinu, Giuseppe Pugliese, Alessandro Passardi, A. Casadei Gardini, S. Vallarelli, M. Libertini, Kalliopi Andrikou, Chiara Manai, Marta Schirripa, N. Silvestris, Floriana Nappo, A. Zaniboni, Giulia Orsi, and Mario Scartozzi
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medicine.medical_specialty ,Oncology ,business.industry ,Adjuvant therapy ,Medicine ,Hematology ,business ,Intensive care medicine ,Outcome (game theory) - Published
- 2018
21. ChemInform Abstract: Synthesis and Characterization of Amino-pyridin-2-yl-methyl-phosphonic Acids
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Paolo Finocchiaro, Salvatore Failla, M. Libertini, and Mario Latronico
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Chemistry ,Organic chemistry ,General Medicine ,Characterization (materials science) - Published
- 2010
22. DELM image processing for skin melanoma early diagnosis
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G. Codagnone, Gianfranco F. Dacquino, M. Crivellini, M. Libertini, A. Morresi, and Rodolfo A. Fiorini
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Image quality ,business.industry ,ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION ,Image processing ,Maximization ,computer.software_genre ,Digital image ,Information extraction ,Geography ,Signal-to-noise ratio ,Feature (computer vision) ,Computer-aided ,Computer vision ,Artificial intelligence ,business ,computer - Abstract
Among the various skin diseases skin tumors are the most serious ones and skin Melanoma is particularly dangerous. Its malignant evolution lasts about 5 or 6 years and ends with the death of the patient. Early diagnosis is a powerful means of preventing this evolution allowing sudden intervention, which increases probability or recover and survival. Aim of the paper is to present the result of an active support system for early diagnosis of melanoma and related skin diseases. The system is based upon a digital acquisition camera with a dedicated illumination system digitally controlled in order to achieve best performance in color and feature discrimination reaching best signal to noise ratio especially in blue band. A polarization framework allows for reflected ray rejection maximization. A new classification approach is presented. It allows for a quantification of morphological patterns and standard parameters in order to implement a computer aided dermatological system. The image information extraction is based on minimal descriptor set of parameters in order to classify chromatic texture and morphological features. The results obtained allow for determination of standard reference grids for pathological cases and reliable and objective classification procedure. We adopt, as reference, the approach used by Stanganelli and Kenet. Through a bioengineering analysis we can organize reference grids that offer the possibility to extract the maximum information content from dermatological data. The classification takes into account the spread and intrinsic descriptors and correspond to the best operative description. Therefore these grids are the more suitable tools for applications which requires active support system for diagnosis. In fact it is possible to obtain quantitative evaluations too. We propose a method based on geometrical synthetical descriptors. All that permits a reliable early diagnosis of melanotic disease and to follow its evolution in time. The first result and the incoming work points to the realization of a system for general dermatological applications.
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- 1997
23. Skin melanoma tracking by DELM active support system
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G. Codagnone, A. Morresi, G. M. De Biase, G. L. Testa, Rodolfo A. Fiorini, M. Crivellini, Gianfranco F. Dacquino, and M. Libertini
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Medical diagnostic ,business.industry ,Classification procedure ,Computer aid ,Quantitative Evaluations ,Machine learning ,computer.software_genre ,Geography ,Tissue optics ,Support system ,Artificial intelligence ,Skin melanoma ,business ,computer ,Active support ,Cartography - Abstract
Skin melanoma tracking by DELM active support systemR.A. Fiorini,Bioengineering Dept., Politecnic of Milan, ItalyM. Crivellini,Bioengineering Dept., Politecnic ofMilan, ItalyG. Codagnone,Dermatological Dept. INRCA,Ancona,ItalyG.F. Dacquino,Bioengineering Dept., Politecnic of Milan, ItalyG.M. De Biase,Bioengineering Dept., Politecnic of Milan, ItalyG. Libertini,Dermatological Dept. [NRCA,Ancona,ItalyA. Morresi,Dermatological Dept. INRCA,Ancona,ItalyG.L. TestaBioengineering Dept., Politecnic of Milan, ItalyABSTRACTThis work refers to the development of an equipment for Computer Assisted Digital Dermatology (CADD) as a basis for thecreation ofActive Support Systems (ASS) for early diagnosis ofmelanotic disease. It is based on a Digital Epiluminescence(DELM) tecnique, taking advantage ofpolarized light guided by optical fibers. In the purpose to dicriminate betweenmalignant and benign melanocytic lesions, several dermatoscopical features have been proposed by different researchgroups. Nevertheless many are the attempts to reach a reliable and objective classification procedure. We adopt, as reference,the approach used by Stanganelli and Kenet. Through a bioengineering analyisis we can organize reference grids that offerthe possibility to extract the maximum information content from dermatological data. The classification takes into accountthe Spread (local, point size, global) and Intrinsic Descriptors (morphological, geometric, chromatic, others) and correspondsto the best operative description. Therefore these grids are the more suitable tools for applications which require ASS fordiagnosis. Infact it is possible to obtain quantitative evaluations too. We propose a method based on Geometrical SynteticalDescriptors. All that permits a reliable early diagnosis ofmelanotic disease and to follow its evolution in time.
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- 1997
24. Effective chromatic texture coding for robust skin disease minimal descriptor quantification
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Gianfranco F. Dacquino, M. Libertini, M. Crivellini, Rodolfo A. Fiorini, G. Codagnone, and A. Morresi
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Dermatoscopy ,medicine.diagnostic_test ,business.industry ,Image quality ,Digital imaging ,Pattern recognition ,computer.software_genre ,Set (abstract data type) ,Information extraction ,Geography ,Robustness (computer science) ,Encoding (memory) ,medicine ,Artificial intelligence ,Chromatic scale ,business ,computer - Abstract
Among the various skin diseases skin tumors are the most serious ones and skin melanoma is particularly dangerous. Its malignant evolution lasts about 5 or 6 years and ends with the death of the patient. Early diagnosis is a powerful means of preventing this evolution allowing sudden intervention which increases probability of recover and survival. Purpose of this paper is to present an active support system (ASS) able to reveal and quantify the stage of disease evolution. The work focuses the problem encountered in chromatic information encoding the morphological aspects quantification. A new method is proposed which permits robust and reliable quantification of image data obtained via a digital epiluminescence dermatoscopy apparatus (DELM) designed and built with interesting new features. The image information extraction is based on minimal descriptor set of parameters in order to classify chromatic texture and morphological features. The active support systems is based on DELM technique, taking advantage of polarized light guided by optical fibers. In the purpose to discriminate between malignant and benign melanocytic lesions, several dermatoscopical features have been proposed by different research groups. Nevertheless many are the attempts to reach a reliable and objective classification procedure. We adopt, as reference, the approach used by Stanganelli and Kenet. Through a bioengineering analysis we can organize reference grids that offer the possibility to extract the maximum information content from dermatological data. The classification takes into account the Spread and Intrinsic Descriptors and correspond to the best operative description. Therefore these grids are the more suitable tools for application which require ASS for diagnosis. In fact it is possible to obtain quantitative evaluations too. We propose a method based on geometrical synthetical descriptors. All that permits a reliable early diagnosis of melanotic disease and to follow its evolution in time. The results obtained allow for disease classification procedure with determination of reference grids for pathological cases and ultimately permits effective early diagnosis of melanotic disease and its follow-up. The first results and the incoming work points to the realization of an Automatic Support System for general dermatological applications.3034© (1997) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
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- 1997
25. Determining tumor blood flow parameters from dynamic image measurements
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Jessica M Libertini
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Alternative methods ,History ,business.industry ,Blood flow ,Plasma volume ,Measure (mathematics) ,Computer Science Applications ,Education ,Image (mathematics) ,Medical imaging ,Medicine ,business ,Focus (optics) ,Perfusion ,Biomedical engineering - Abstract
Many recent cancer treatments focus on preventing angiogenesis, the process by which a tumor promotes the growth of large and efficient capillary beds for the increased nourishment required to support the tumor's rapid growth[l]. To measure the efficacy of these treatments in a timely fashion, there is an interest in using data from dynamic sequences of contrast-enhanced medical imaging, such as MRI and CT, to measure blood flow parameters such as perfusion, permeability-surface-area product, and the relative volumes of the plasma and extracellular-extravascular space. Starting with a two compartment model presented by the radiology community[2], this work challenges the application of a simplification to this problem, which was originally developed to model capillary reuptake[3]. While the primary result of this work is the demonstration of the inaccuracy of this simplification, the remainder of the paper is dedicated to presenting alternative methods for calculating the perfusion and plasma volume coefficients. These methods are applied to model data sets based on real patient data, and preliminary results are presented.
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- 2008
26. Teaching Calculus as a Tool in the Twenty-First Century
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Zbarsky, Emma Smith, Simundza, Gary, Henriksen, Mel, Formaggia, Luca, Editor-in-Chief, Pedregal, Pablo, Editor-in-Chief, Larson, Mats G., Series Editor, Martínez-Seara Alonso, Tere, Series Editor, Parés, Carlos, Series Editor, Pareschi, Lorenzo, Series Editor, Tosin, Andrea, Series Editor, Vázquez-Cendón, Elena, Series Editor, Zunino, Paolo, Series Editor, Buckmire, Ron, editor, and M. Libertini, Jessica, editor
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- 2021
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27. Developing Non-Calculus Service Courses That Showcase the Applicability of Mathematics
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Castle, Lucas, Formaggia, Luca, Editor-in-Chief, Pedregal, Pablo, Editor-in-Chief, Larson, Mats G., Series Editor, Martínez-Seara Alonso, Tere, Series Editor, Parés, Carlos, Series Editor, Pareschi, Lorenzo, Series Editor, Tosin, Andrea, Series Editor, Vázquez-Cendón, Elena, Series Editor, Zunino, Paolo, Series Editor, Buckmire, Ron, editor, and M. Libertini, Jessica, editor
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- 2021
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28. Promoting Interdisciplinary and Mathematical Modelling Through Competitions
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Kushnarev, Sergey, Libertini, Jessica M., Formaggia, Luca, Editor-in-Chief, Pedregal, Pablo, Editor-in-Chief, Larson, Mats G., Series Editor, Martínez-Seara Alonso, Tere, Series Editor, Parés, Carlos, Series Editor, Pareschi, Lorenzo, Series Editor, Tosin, Andrea, Series Editor, Vázquez-Cendón, Elena, Series Editor, Zunino, Paolo, Series Editor, Buckmire, Ron, editor, and M. Libertini, Jessica, editor
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- 2021
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29. Engaging Students in Applied Mathematics Education and Research for Global Problem Solving
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Wang, Wei, Seshaiyer, Padmanabhan, Formaggia, Luca, Editor-in-Chief, Pedregal, Pablo, Editor-in-Chief, Larson, Mats G., Series Editor, Martínez-Seara Alonso, Tere, Series Editor, Parés, Carlos, Series Editor, Pareschi, Lorenzo, Series Editor, Tosin, Andrea, Series Editor, Vázquez-Cendón, Elena, Series Editor, Zunino, Paolo, Series Editor, Buckmire, Ron, editor, and M. Libertini, Jessica, editor
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- 2021
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30. 'Who Does the Math?': On the Diversity and Demographics of the Mathematics Community in the USA
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Buckmire, Ron, Formaggia, Luca, Editor-in-Chief, Pedregal, Pablo, Editor-in-Chief, Larson, Mats G., Series Editor, Martínez-Seara Alonso, Tere, Series Editor, Parés, Carlos, Series Editor, Pareschi, Lorenzo, Series Editor, Tosin, Andrea, Series Editor, Vázquez-Cendón, Elena, Series Editor, Zunino, Paolo, Series Editor, Buckmire, Ron, editor, and M. Libertini, Jessica, editor
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- 2021
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31. Adverse events during first-line treatments for mCRC: The Toxicity over Time (ToxT) analysis of three randomised trials.
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Boccaccino A, Rossini D, Raimondi A, Carullo M, Lonardi S, Morano F, Santini D, Tomasello G, Niger M, Zaniboni A, Daniel F, Bustreo S, Procaccio L, Clavarezza M, Cupini S, Libertini M, Palermo F, Pietrantonio F, and Cremolini C
- Subjects
- Humans, Bevacizumab, Panitumumab therapeutic use, Camptothecin, Fluorouracil, Antineoplastic Combined Chemotherapy Protocols adverse effects, Leucovorin, Colorectal Neoplasms drug therapy, Colorectal Neoplasms pathology, Colonic Neoplasms drug therapy, Rectal Neoplasms drug therapy
- Abstract
Background: In clinical trials, the assessment of safety is traditionally focused on the overall rate of high-grade and serious adverse events (AEs). A new approach to AEs evaluation, taking into account chronic low-grade AEs, single patient's perspective, and time-related information, such as ToxT analysis, should be considered especially for less intense but potentially long-lasting treatments, such as maintenance strategies in metastatic colorectal cancer (mCRC)., Patients and Methods: We applied ToxT (Toxicity over Time) evaluation to a large cohort of mCRC patients enroled in randomised TRIBE, TRIBE2, and VALENTINO studies, in order to longitudinally describe AEs throughout the whole treatment duration and to compare AEs evolution over cycles between induction and maintenance strategies, providing numerical and graphical results overall and per single patient. After 4-6 months of combination therapy, 5-fluorouracil/leucovorin (5-FU/LV) + bevacizumab or panitumumab was recommended in all studies except for the 50% of patients in the VALENTINO trial who received panitumumab alone., Results: Out of 1400 patients included, 42% received FOLFOXIRI (5-FU/LV, oxaliplatin, and irinotecan)/bevacizumab, 18% FOLFIRI/bevacizumab, 24% FOLFOX/bevacizumab, 16% FOLFOX/panitumumab. Mean grade of general and haematological AEs was higher in the first cycles, then progressively decreasing after the end of induction (p < 0.001), and always remaining at the highest levels with FOLFOXIRI/bevacizumab (p < 0.001). Neurotoxicity became more frequent over the cycles with late high-grade episodes (p < 0.001), while the incidence but not the grade of hand-and-foot syndrome gradually increased (p = 0.91). Anti-VEGF-related AEs were more severe in the first cycles, then setting over at low levels (p = 0.03), while anti-EGFR-related AEs still affected patients during maintenance., Conclusions: Most of chemotherapy-related AEs (except for HFS and neuropathy) reach the highest level in the first cycles, then decrease, probably due to their active clinical management. Transition to maintenance allows relief from most AEs, especially with bevacizumab-based regimens, while anti-EGFR-related AEs may persist., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AR: Honoraria for speaker bureau for Servier and Elma Academy. FM: Honoraria from Servier, Pierre-Fabre and Lilly; Research grant from Incyte.GT: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Eli Lilly, Novartis, Amgen, Roche, Merck; Participation on a Data Safety Monitoring Board or Advisory Board: Eli Lilly, Amgen, Roche. MN: Travel expenses from Celgene and AstraZeneca; Speaker honorarium from Accademia della Medicina and Incyte; Honoraria from Sandoz, Medpoint SRL and Servier for editorial collaboration; Consultant honoraria from EMD Serono, Basilea Pharmaceutica, Incyte, MSD Italia, Servier, Astrazeneca and Taiho. AZ: Speaker Bureau for Amgen, Merck-Serono, Servier, Pierre-Fabre. FP: Honoraria from Amgen, Bayer, Servier, Merck-Serono, Lilly, MSD, Organon, BMS, Astrazeneca, Pierre-Fabre; Research grants from Bristol-Myers Squibb, AstraZeneca, Agenus and Incyte. CC: Honoraria from Amgen, Bayer, Merck, Roche and Servier; Consulting or advisory role: Amgen, Bayer, MSD, Roche; Speakers’ Bureau: Servier; Research funding: Bayer, Merck, Servier; Travel accommodations and expenses: Roche and Servier. All the other authors have declared no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
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- 2023
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32. Pandemic Phase-Adjusted Analysis of COVID-19 Outcomes Reveals Reduced Intrinsic Vulnerability and Substantial Vaccine Protection From Severe Acute Respiratory Syndrome Coronavirus 2 in Patients With Breast Cancer.
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Tagliamento M, Gennari A, Lambertini M, Salazar R, Harbeck N, Del Mastro L, Aguilar-Company J, Bower M, Sharkey R, Dalla Pria A, Plaja A, Jackson A, Handford J, Sita-Lumsden A, Martinez-Vila C, Matas M, Miguel Rodriguez A, Vincenzi B, Tonini G, Bertuzzi A, Brunet J, Pedrazzoli P, D'Avanzo F, Biello F, Sinclair A, Lee AJX, Rossi S, Rizzo G, Mirallas O, Pimentel I, Iglesias M, Sanchez de Torre A, Guida A, Berardi R, Zambelli A, Tondini C, Filetti M, Mazzoni F, Mukherjee U, Diamantis N, Parisi A, Aujayeb A, Prat A, Libertini M, Grisanti S, Rossi M, Zoratto F, Generali D, Saura C, Lyman GH, Kuderer NM, Pinato DJ, and Cortellini A
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- Humans, Middle Aged, Female, SARS-CoV-2, COVID-19 Testing, Pandemics, COVID-19 epidemiology, COVID-19 prevention & control, Breast Neoplasms epidemiology, Breast Neoplasms therapy, Vaccines
- Abstract
Purpose: Although representing the majority of newly diagnosed cancers, patients with breast cancer appear less vulnerable to COVID-19 mortality compared with other malignancies. In the absence of patients on active cancer therapy included in vaccination trials, a contemporary real-world evaluation of outcomes during the various pandemic phases, as well as of the impact of vaccination, is needed to better inform clinical practice., Methods: We compared COVID-19 morbidity and mortality among patients with breast cancer across prevaccination (February 27, 2020-November 30, 2020), Alpha-Delta (December 1, 2020-December 14, 2021), and Omicron (December 15, 2021-January 31, 2022) phases using OnCovid registry participants (ClinicalTrials.gov identifier: NCT04393974). Twenty-eight-day case fatality rate (CFR
28 ) and COVID-19 severity were compared in unvaccinated versus double-dosed/boosted patients (vaccinated) with inverse probability of treatment weighting models adjusted for country of origin, age, number of comorbidities, tumor stage, and receipt of systemic anticancer therapy within 1 month of COVID-19 diagnosis., Results: By the data lock of February 4, 2022, the registry counted 613 eligible patients with breast cancer: 60.1% (n = 312) hormone receptor-positive, 25.2% (n = 131) human epidermal growth factor receptor 2-positive, and 14.6% (n = 76) triple-negative. The majority (61%; n = 374) had localized/locally advanced disease. Median age was 62 years (interquartile range, 51-74 years). A total of 193 patients (31.5%) presented ≥ 2 comorbidities and 69% (n = 330) were never smokers. In total, 392 (63.9%), 164 (26.8%), and 57 (9.3%) were diagnosed during the prevaccination, Alpha-Delta, and Omicron phases, respectively. Analysis of CFR28 demonstrates comparable estimates of mortality across the three pandemic phases (13.9%, 12.2%, 5.3%, respectively; P = .182). Nevertheless, a significant improvement in outcome measures of COVID-19 severity across the three pandemic time periods was observed. Importantly, when reported separately, unvaccinated patients from the Alpha-Delta and Omicron phases achieved comparable outcomes to those from the prevaccination phase. Of 566 patients eligible for the vaccination analysis, 72 (12.7%) were fully vaccinated and 494 (87.3%) were unvaccinated. We confirmed with inverse probability of treatment weighting multivariable analysis and following a clustered robust correction for participating center that vaccinated patients achieved improved CFR28 (odds ratio [OR], 0.19; 95% CI, 0.09 to 0.40), hospitalization (OR, 0.28; 95% CI, 0.11 to 0.69), COVID-19 complications (OR, 0.16; 95% CI, 0.06 to 0.45), and reduced requirement of COVID-19-specific therapy (OR, 0.24; 95% CI, 0.09 to 0.63) and oxygen therapy (OR, 0.24; 95% CI, 0.09 to 0.67) compared with unvaccinated controls., Conclusion: Our findings highlight a consistent reduction of COVID-19 severity in patients with breast cancer during the Omicron outbreak in Europe. We also demonstrate that even in this population, a complete severe acute respiratory syndrome coronavirus 2 vaccination course is a strong determinant of improved morbidity and mortality from COVID-19.- Published
- 2023
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33. Codon-specific KRAS mutations predict survival benefit of trifluridine/tipiracil in metastatic colorectal cancer.
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van de Haar J, Ma X, Ooft SN, van der Helm PW, Hoes LR, Mainardi S, Pinato DJ, Sun K, Salvatore L, Tortora G, Zurlo IV, Leo S, Giampieri R, Berardi R, Gelsomino F, Merz V, Mazzuca F, Antonuzzo L, Rosati G, Stavraka C, Ross P, Rodriquenz MG, Pavarana M, Messina C, Iveson T, Zoratto F, Thomas A, Fenocchio E, Ratti M, Depetris I, Cergnul M, Morelli C, Libertini M, Parisi A, De Tursi M, Zanaletti N, Garrone O, Graham J, Longarini R, Gobba SM, Petrillo A, Tamburini E, La Verde N, Petrelli F, Ricci V, Wessels LFA, Ghidini M, Cortellini A, Voest EE, and Valeri N
- Subjects
- Humans, Proto-Oncogene Proteins p21(ras) genetics, Uracil therapeutic use, Trifluridine therapeutic use, Pyrrolidines therapeutic use, Drug Combinations, Mutation genetics, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Colorectal Neoplasms drug therapy, Colorectal Neoplasms genetics, Frontotemporal Dementia, Colonic Neoplasms drug therapy, Rectal Neoplasms drug therapy
- Abstract
Genomics has greatly improved how patients with cancer are being treated; however, clinical-grade genomic biomarkers for chemotherapies are currently lacking. Using whole-genome analysis of 37 patients with metastatic colorectal cancer (mCRC) treated with the chemotherapy trifluridine/tipiracil (FTD/TPI), we identified KRAS codon G12 (KRAS
G12 ) mutations as a potential biomarker of resistance. Next, we collected real-world data of 960 patients with mCRC receiving FTD/TPI and validated that KRASG12 mutations were significantly associated with poor survival, also in analyses restricted to the RAS/RAF mutant subgroup. We next analyzed the data of the global, double-blind, placebo-controlled, phase 3 RECOURSE trial (n = 800 patients) and found that KRASG12 mutations (n = 279) were predictive biomarkers for reduced overall survival (OS) benefit of FTD/TPI versus placebo (unadjusted interaction P = 0.0031, adjusted interaction P = 0.015). For patients with KRASG12 mutations in the RECOURSE trial, OS was not prolonged with FTD/TPI versus placebo (n = 279; hazard ratio (HR) = 0.97; 95% confidence interval (CI) = 0.73-1.20; P = 0.85). In contrast, patients with KRASG13 mutant tumors showed significantly improved OS with FTD/TPI versus placebo (n = 60; HR = 0.29; 95% CI = 0.15-0.55; P < 0.001). In isogenic cell lines and patient-derived organoids, KRASG12 mutations were associated with increased resistance to FTD-based genotoxicity. In conclusion, these data show that KRASG12 mutations are biomarkers for reduced OS benefit of FTD/TPI treatment, with potential implications for approximately 28% of patients with mCRC under consideration for treatment with FTD/TPI. Furthermore, our data suggest that genomics-based precision medicine may be possible for a subset of chemotherapies., (© 2023. The Author(s).)- Published
- 2023
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34. COVID-19 Sequelae and the Host Proinflammatory Response: An Analysis From the OnCovid Registry.
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Cortellini A, Gennari A, Pommeret F, Patel G, Newsom-Davis T, Bertuzzi A, Viladot M, Aguilar-Company J, Mirallas O, Felip E, Lee AJX, Dalla Pria A, Sharkey R, Brunet J, Carmona-García M, Chester J, Mukherjee U, Scotti L, Dolly S, Sita-Lumsden A, Ferrante D, Van Hemelrijck M, Moss C, Russell B, Seguí E, Biello F, Krengli M, Marco-Hernández J, Gaidano G, Patriarca A, Bruna R, Roldán E, Fox L, Pous A, Griscelli F, Salazar R, Martinez-Vila C, Sureda A, Loizidou A, Maluquer C, Stoclin A, Iglesias M, Pedrazzoli P, Rizzo G, Santoro A, Rimassa L, Rossi S, Harbeck N, Sanchez de Torre A, Vincenzi B, Libertini M, Provenzano S, Generali D, Grisanti S, Berardi R, Tucci M, Mazzoni F, Lambertini M, Tagliamento M, Parisi A, Zoratto F, Queirolo P, Giusti R, Guida A, Zambelli A, Tondini C, Maconi A, Betti M, Colomba E, Diamantis N, Sinclair A, Bower M, Ruiz-Camps I, and Pinato DJ
- Subjects
- C-Reactive Protein analysis, COVID-19 Testing, Disease Progression, Humans, Lactate Dehydrogenases, Lymphocytes chemistry, Neutrophils chemistry, Prognosis, ROC Curve, Registries, Retrospective Studies, COVID-19 complications, COVID-19 epidemiology
- Abstract
Background: Fifteen percent of patients with cancer experience symptomatic sequelae, which impair post-COVID-19 outcomes. In this study, we investigated whether a proinflammatory status is associated with the development of COVID-19 sequelae., Methods: OnCovid recruited 2795 consecutive patients who were diagnosed with Severe Acute Respiratory Syndrome Coronavirus 2 infection between February 27, 2020, and February 14, 2021. This analysis focused on COVID-19 survivors who underwent a clinical reassessment after the exclusion of patients with hematological malignancies. We evaluated the association of inflammatory markers collected at COVID-19 diagnosis with sequelae, considering the impact of previous systemic anticancer therapy. All statistical tests were 2-sided., Results: Of 1339 eligible patients, 203 experienced at least 1 sequela (15.2%). Median baseline C-reactive protein (CRP; 77.5 mg/L vs 22.2 mg/L, P < .001), lactate dehydrogenase (310 UI/L vs 274 UI/L, P = .03), and the neutrophil to lymphocyte ratio (NLR; 6.0 vs 4.3, P = .001) were statistically significantly higher among patients who experienced sequelae, whereas no association was reported for the platelet to lymphocyte ratio and the OnCovid Inflammatory Score, which includes albumin and lymphocytes. The widest area under the ROC curve (AUC) was reported for baseline CRP (AUC = 0.66, 95% confidence interval [CI]: 0.63 to 0.69), followed by the NLR (AUC = 0.58, 95% CI: 0.55 to 0.61) and lactate dehydrogenase (AUC = 0.57, 95% CI: 0.52 to 0.61). Using a fixed categorical multivariable analysis, high CRP (odds ratio [OR] = 2.56, 95% CI: 1.67 to 3.91) and NLR (OR = 1.45, 95% CI: 1.01 to 2.10) were confirmed to be statistically significantly associated with an increased risk of sequelae. Exposure to chemotherapy was associated with a decreased risk of sequelae (OR = 0.57, 95% CI: 0.36 to 0.91), whereas no associations with immune checkpoint inhibitors, endocrine therapy, and other types of systemic anticancer therapy were found., Conclusions: Although the association between inflammatory status, recent chemotherapy and sequelae warrants further investigation, our findings suggest that a deranged proinflammatory reaction at COVID-19 diagnosis may predict for sequelae development., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2022
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35. Outcomes of the SARS-CoV-2 omicron (B.1.1.529) variant outbreak among vaccinated and unvaccinated patients with cancer in Europe: results from the retrospective, multicentre, OnCovid registry study.
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Pinato DJ, Aguilar-Company J, Ferrante D, Hanbury G, Bower M, Salazar R, Mirallas O, Sureda A, Plaja A, Cucurull M, Mesia R, Townsend S, Jackson A, Dalla Pria A, Newsom-Davis T, Handford J, Sita-Lumsden A, Apthorp E, Vincenzi B, Bertuzzi A, Brunet J, Lambertini M, Maluquer C, Pedrazzoli P, Biello F, Sinclair A, Bawany S, Khalique S, Rossi S, Rogers L, Murphy C, Belessiotis K, Carmona-García MC, Sharkey R, García-Illescas D, Rizzo G, Perachino M, Saoudi-Gonzalez N, Doonga K, Fox L, Roldán E, Gaidano G, Ruiz-Camps I, Bruna R, Patriarca A, Martinez-Vila C, Cantini L, Zambelli A, Giusti R, Mazzoni F, Caliman E, Santoro A, Grosso F, Parisi A, Queirolo P, Aujayeb A, Rimassa L, Prat A, Tucci M, Libertini M, Grisanti S, Mukherjee U, Diamantis N, Fusco V, Generali D, Provenzano S, Gennari A, Tabernero J, and Cortellini A
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- Aged, COVID-19 Testing, Disease Outbreaks, Europe epidemiology, Female, Humans, Male, Middle Aged, Oxygen, Registries, Retrospective Studies, SARS-CoV-2, COVID-19 epidemiology, COVID-19 prevention & control, Neoplasms epidemiology, Neoplasms therapy
- Abstract
Background: The omicron (B.1.1.529) variant of SARS-CoV-2 is highly transmissible and escapes vaccine-induced immunity. We aimed to describe outcomes due to COVID-19 during the omicron outbreak compared with the prevaccination period and alpha (B.1.1.7) and delta (B.1.617.2) waves in patients with cancer in Europe., Methods: In this retrospective analysis of the multicentre OnCovid Registry study, we recruited patients aged 18 years or older with laboratory-confirmed diagnosis of SARS-CoV-2, who had a history of solid or haematological malignancy that was either active or in remission. Patient were recruited from 37 oncology centres from UK, Italy, Spain, France, Belgium, and Germany. Participants were followed up from COVID-19 diagnosis until death or loss to follow-up, while being treated as per standard of care. For this analysis, we excluded data from centres that did not actively enter new data after March 1, 2021 (in France, Germany, and Belgium). We compared measures of COVID-19 morbidity, which were complications from COVID-19, hospitalisation due to COVID-19, and requirement of supplemental oxygen and COVID-19-specific therapies, and COVID-19 mortality across three time periods designated as the prevaccination (Feb 27 to Nov 30, 2020), alpha-delta (Dec 1, 2020, to Dec 14, 2021), and omicron (Dec 15, 2021, to Jan 31, 2022) phases. We assessed all-cause case-fatality rates at 14 days and 28 days after diagnosis of COVID-19 overall and in unvaccinated and fully vaccinated patients and in those who received a booster dose, after adjusting for country of origin, sex, age, comorbidities, tumour type, stage, and status, and receipt of systemic anti-cancer therapy. This study is registered with ClinicalTrials.gov, NCT04393974, and is ongoing., Findings: As of Feb 4, 2022 (database lock), the registry included 3820 patients who had been diagnosed with COVID-19 between Feb 27, 2020, and Jan 31, 2022. 3473 patients were eligible for inclusion (1640 [47·4%] were women and 1822 [52·6%] were men, with a median age of 68 years [IQR 57-77]). 2033 (58·5%) of 3473 were diagnosed during the prevaccination phase, 1075 (31·0%) during the alpha-delta phase, and 365 (10·5%) during the omicron phase. Among patients diagnosed during the omicron phase, 113 (33·3%) of 339 were fully vaccinated and 165 (48·7%) were boosted, whereas among those diagnosed during the alpha-delta phase, 152 (16·6%) of 915 were fully vaccinated and 21 (2·3%) were boosted. Compared with patients diagnosed during the prevaccination period, those who were diagnosed during the omicron phase had lower case-fatality rates at 14 days (adjusted odds ratio [OR] 0·32 [95% CI 0·19-0·61) and 28 days (0·34 [0·16-0·79]), complications due to COVID-19 (0·26 [0·17-0·46]), and hospitalisation due to COVID-19 (0·17 [0·09-0·32]), and had less requirements for COVID-19-specific therapy (0·22 [0·15-0·34]) and oxygen therapy (0·24 [0·14-0·43]) than did those diagnosed during the alpha-delta phase. Unvaccinated patients diagnosed during the omicron phase had similar crude case-fatality rates at 14 days (ten [25%] of 40 patients vs 114 [17%] of 656) and at 28 days (11 [27%] of 40 vs 184 [28%] of 656) and similar rates of hospitalisation due to COVID-19 (18 [43%] of 42 vs 266 [41%] of 652) and complications from COVID-19 (13 [31%] of 42 vs 237 [36%] of 659) as those diagnosed during the alpha-delta phase., Interpretation: Despite time-dependent improvements in outcomes reported in the omicron phase compared with the earlier phases of the pandemic, patients with cancer remain highly susceptible to SARS-CoV-2 if they are not vaccinated against SARS-CoV-2. Our findings support universal vaccination of patients with cancer as a protective measure against morbidity and mortality from COVID-19., Funding: National Institute for Health and Care Research Imperial Biomedical Research Centre and the Cancer Treatment and Research Trust., Competing Interests: Declaration of interests DJP has received lecture fees from ViiV Healthcare, Bayer Healthcare, BMS, Roche, Eisai, and Falk Foundation; travel expenses from BMS and Bayer Healthcare; consulting fees for Mina Therapeutics, Eisai, Roche, DaVolterra, and Astra Zeneca; and research funding (to their institution) from MSD and BMS. MLa has acted as consultant for Roche, Novartis, Lilly, AstraZeneca, Exact Sciences, MSD, Pfizer, Seagen, and Gilead; and has received speaker honoraria from Roche, Novartis, Lilly, Pfizer, Takeda, Ipsen, Libbs, Knight, and Sandoz. FM has received consulting fees from Eli Lilly, MSD, Takeda, and Roche; and travel support from Sanofi. SP reported that their spouse is employed by AstraZeneca. ASa has received consulting fees from Arqule, Sanofi, and Incyte; speaker's fees from Takeda, BMS, Roche, AbbVie, Amgen, Celgene, Servier, Gilead, AstraZeneca, Pfizer, Arqule, Eli Lilly, Sandoz, Eisai, Novartis, Bayer, and MSD; and participation on data monitoring committees for BMS, Servier, Gilead, Pfizer, Eisai, Bayer, and MSD. FG has received consulting fees from Novocure, BMS, PharmaMar, and Novartis; speaker's fees from Novocure; travel support from MSD, Novocure, BMS, Boehringer Ingelheim, PharmaMar, Novartis, and Pierre Fabre; and participation on a data safety monitoring board for MSD, BMS, PharmaMar and Novartis. JH has a leadership role with Blood Cancer UK. NS-G has received speakers' fees from Amgen. GG has received consulting fees or had an advisory role for Janssen, AbbVie, AstraZeneca, Roche, Incyte, and BeiGene, and reported speaker fees from Janssen and AbbVie. LRi has received consulting fees from Taiho Oncology, Servier, Amgen, ArQule, AstraZeneca, Basilea, Bayer, BMS, Celgene, Eisai, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Lilly, MSD, Nerviano Medical Sciences, Roche, Sanofi, and Zymeworks; lecture fees from AbbVie, Amgen, Bayer, Eisai, Gilead, Incyte, Ipsen, Lilly, Merck Serono, Roche, and Sanofi; travel expenses from Ipsen; and institutional research funding from Agios, ARMO BioSciences, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, and Zymeworks. JT reports consulting fees from Array Biopharma, AstraZeneca, Avvinity, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F Hoffmann-La Roche, Genentech, HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, Inspirna, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Ona Therapeutics, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Scandion Oncology, Servier, Sotio Biotech, Taiho, Tessa Therapeutics, and TheraMyc; speaker's fees from Imedex, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education, and Physicians Education Resource; and institutional research support from Amgen, Array Biopharma, AstraZeneca Pharmaceuticals, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Debiopharm International, F Hoffmann-La Roche, Genentech, HalioDX, Hutchison MediPharma International, Janssen-Cilag, MedImmune, Menarini, Merck Health, Merck Sharp & Dohme, Merus NV, Mirati, Novartis Farmacéutica, Pfizer, Pharma Mar, Sanofi Aventis Recherche & Développement, Servier, Taiho Pharma USA, Spanish Association Against Cancer Scientific Foundation, and Cancer Research UK. MB has received speakers' fee from Eisai pharma, Gilead Sciences, Merck, and ViiV; and has had leadership roles in the European AIDS Clinical Society, UNAIDS, WHO, and The European Hematology Association/ European Society of Medical Oncology. AC has received consulting fees from MSD, BMS, AstraZeneca, and Roche; and speakers' fee from AstraZeneca, MSD, Novartis, and Eisai. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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36. Encorafenib plus cetuximab with or without binimetinib in patients with BRAF V600E-mutated metastatic colorectal cancer: real-life data from an Italian multicenter experience.
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Boccaccino A, Borelli B, Intini R, Antista M, Bensi M, Rossini D, Passardi A, Tamberi S, Giampieri R, Antonuzzo L, Noto L, Roviello G, Zichi C, Salati M, Puccini A, Noto C, Parisi A, Rihawi K, Persano M, Crespi V, Libertini M, Giordano M, Moretto R, Lonardi S, and Cremolini C
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- Antineoplastic Combined Chemotherapy Protocols adverse effects, Benzimidazoles, Carbamates, Cetuximab adverse effects, Humans, Proto-Oncogene Proteins B-raf genetics, Sulfonamides, Colonic Neoplasms drug therapy, Colorectal Neoplasms drug therapy, Colorectal Neoplasms genetics
- Abstract
Background: Encorafenib plus cetuximab with or without binimetinib showed increased objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) compared with chemotherapy plus anti-EGFR in previously treated patients with BRAF V600E-mutated (mut) metastatic colorectal cancer (mCRC). Although no formal comparison was planned, addition of binimetinib to encorafenib plus cetuximab did not provide significant efficacy advantage., Patients and Methods: This real-life study was aimed at evaluating safety, activity, and efficacy of encorafenib plus cetuximab with or without binimetinib in patients with BRAF V600E-mut mCRC treated at 21 Italian centers within a nominal use program launched in May 2019., Results: Out of 133 patients included, 97 (73%) received encorafenib plus cetuximab (targeted doublet) and 36 (27%) the same therapy plus binimetinib (targeted triplet). Most patients had Eastern Cooperative Group Performance Status (ECOG-PS) of 0 or 1 (86%), right-sided primary tumor (69%), and synchronous disease (66%). Twenty (15%) tumors were DNA mismatch repair deficiency (dMMR)/microsatellite instability (MSI)-high. As many as 44 (34%) patients had received two or more prior lines of therapy, 122 (92%) were previously exposed to oxaliplatin, and 109 (82%) to anti-vascular endothelial growth factor (anti-VEGF). Most frequent adverse events were asthenia (62%) and anti-EGFR-related skin rash (52%). Any grade nausea (P = 0.03), vomiting (P = 0.04), and diarrhea (P = 0.07) were more frequent with the triplet therapy, while melanocytic nevi were less common (P = 0.06). Overall, ORR and disease control rate (DCR) were 23% and 69%, respectively, with numerically higher rates in the triplet group (ORR 31% versus 17%, P = 0.12; DCR 78% versus 65%, P = 0.23). Median PFS and OS were 4.5 and 7.2 months, respectively. Worse ECOG-PS, peritoneal metastases, and more than one prior treatment were independent poor prognostic factors for PFS and OS. Clonality of BRAF mutation measured as adjusted mutant allele fraction in tumor tissue was not associated with clinical outcome., Conclusions: Our real-life data are consistent with those from the BEACON trial in terms of safety, activity, and efficacy. Patients in good general condition and not heavily pretreated are those more likely to derive benefit from the targeted treatment., Competing Interests: Disclosure MS reports being on the advisory board and speakers’ bureau for MERCK, MSD, Sanofi, Amgen, BMS, EISAI, and Servier. SL reports being on the speakers’ bureau for Amgen, Merck, Roche, Lilly, Bristol-Myers Squibb, Pierre-Fabre, GSK, and Servier; playing a consulting or advisory role for Amgen, MSD, Merck Serono, Lilly, Astra Zeneca, Incyte, Daiichi-Sankyo, Bristol-Myers Squibb, and Servier; research funding to institution from Bayer, Merck, Amgen, Roche, Lilly, AstraZeneca, and Bristol-Myers Squibb. CC reports honoraria from Amgen, Bayer, Merck, Roche, and Servier; performing a consulting or advisory role for Amgen, Bayer, MSD, and Roche; being on the speakers’ bureau for Servier; receiving/received research funding from Bayer, Merck, and Servier; travel, accommodations, and expenses from Roche and Servier. All other authors have declared no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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37. Systemic treatment in advanced phyllodes tumor of the breast: a multi-institutional European retrospective case-series analyses.
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Palassini E, Mir O, Grignani G, Vincenzi B, Gelderblom H, Sebio A, Valverde C, Baldi GG, Brunello A, Cardellino GG, Marrari A, Badalamenti G, Martin-Broto J, Ferraresi V, Libertini M, Turano S, Gataa I, Collini P, Tos APD, Gennaro M, Bini F, Provenzano S, Vullo SL, Mariani L, Le Cesne A, and Casali PG
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- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Female, Humans, Middle Aged, Response Evaluation Criteria in Solid Tumors, Retrospective Studies, Breast Neoplasms drug therapy, Sarcoma pathology
- Abstract
Background: We aimed at investigating outcome of systemic treatments in advanced breast PT., Methods: All cases of advanced breast PT treated with systemic treatments from 1999 to 2019, in one of the referral sarcoma centers involved in the study, were retrospectively reviewed., Results: 56 female patients were identified. Median age was 52 (range of 25-76) years. Patients received a median number of 2 systemic treatments (range of 1-4). Best responses according to RECIST were 1 (3.7%) CR, 11 (40.7%) PR, 6 (22.2%) SD, 9 (33.3%) PD with anthracyclines plus ifosfamide (AI); 2 (16.7%) PR, 4 (33.3%) SD, 6 (50.0%) PD with anthracycline alone; 3 (18.8%) PR, 4 (25.0%) SD, 9 (56.3%) PD with high-dose ifosfamide given as a continuous infusion (HD-IFX); 3 (20.0%) SD, 12 (80.0%) PD with a gemcitabine-based regimen (with 2 patients not evaluable); 1 (8.3%) PR, 2 (16.7%) SD, 9 (75.0%) PD with trabectedin (with 1 patient not evaluable); 1 (16.7%) PR, 1 (16.7%) SD, 4 (66.7%) PD with tyrosine-kinase inhibitors (TKI). The median PFS were 5.7 (IQR 2.5-9.1) months with AI; 3.2 (IQR 2.2-5.0) months with anthracycline alone; 3.4 (IQR 1.4-6.7) months with HD-IFX; 2.1 (IQR 1.4-5.2) months with gemcitabine-based chemotherapy; 1.8 (IQR 0.7-6.6) months with trabectedin; 3.4 (IQR 3.1-3.8) months with TKI. With a median follow-up of 35.3 (IQR 17.6-66.9) months, OS from the start of first-line systemic treatment was 15.2 (IQR 7.6-39.6) months., Conclusion: In this series of advanced PT (to our knowledge, the largest reported so far), AI was associated with a high rate of responses, however, with a median PFS of 5.7 months. Other systemic treatments were poorly active., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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38. Time-Dependent COVID-19 Mortality in Patients With Cancer: An Updated Analysis of the OnCovid Registry.
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Pinato DJ, Patel M, Scotti L, Colomba E, Dolly S, Loizidou A, Chester J, Mukherjee U, Zambelli A, Dalla Pria A, Aguilar-Company J, Bower M, Salazar R, Bertuzzi A, Brunet J, Lambertini M, Tagliamento M, Pous A, Sita-Lumsden A, Srikandarajah K, Colomba J, Pommeret F, Seguí E, Generali D, Grisanti S, Pedrazzoli P, Rizzo G, Libertini M, Moss C, Evans JS, Russell B, Harbeck N, Vincenzi B, Biello F, Bertulli R, Ottaviani D, Liñan R, Rossi S, Carmona-García MC, Tondini C, Fox L, Baggi A, Fotia V, Parisi A, Porzio G, Queirolo P, Cruz CA, Saoudi-Gonzalez N, Felip E, Roqué Lloveras A, Newsom-Davis T, Sharkey R, Roldán E, Reyes R, Zoratto F, Earnshaw I, Ferrante D, Marco-Hernández J, Ruiz-Camps I, Gaidano G, Patriarca A, Bruna R, Sureda A, Martinez-Vila C, Sanchez de Torre A, Berardi R, Giusti R, Mazzoni F, Guida A, Rimassa L, Chiudinelli L, Franchi M, Krengli M, Santoro A, Prat A, Tabernero J, Van Hemelrijck M, Diamantis N, Gennari A, and Cortellini A
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- Aged, Female, Humans, Infant, Male, Pandemics, Registries, SARS-CoV-2, COVID-19, Neoplasms epidemiology
- Abstract
Importance: Whether the severity and mortality of COVID-19 in patients with cancer have improved in terms of disease management and capacity is yet to be defined., Objective: To test whether severity and mortality from COVID-19 among patients with cancer have improved during the course of the pandemic., Design, Setting, and Participants: OnCovid is a European registry that collects data on consecutive patients with solid or hematologic cancer and COVID-19. This multicenter case series study included real-world data from 35 institutions across 6 countries (UK, Italy, Spain, France, Belgium, and Germany). This update included patients diagnosed between February 27, 2020, and February, 14, 2021. Inclusion criteria were confirmed diagnosis of SARS-CoV-2 infection and a history of solid or hematologic cancer., Exposures: SARS-CoV-2 infection., Main Outcomes and Measures: Deaths were differentiated at 14 days and 3 months as the 2 landmark end points. Patient characteristics and outcomes were compared by stratifying patients across 5 phases (February to March 2020, April to June 2020, July to September 2020, October to December 2020, and January to February 2021) and across 2 major outbreaks (February to June 2020 and July 2020 to February 2021)., Results: At data cutoff, 2795 consecutive patients were included, with 2634 patients eligible for analysis (median [IQR] age, 68 [18-77] years ; 52.8% men). Eligible patients demonstrated significant time-dependent improvement in 14-day case-fatality rate (CFR) with estimates of 29.8% (95% CI, 0.26-0.33) for February to March 2020; 20.3% (95% CI, 0.17-0.23) for April to June 2020; 12.5% (95% CI, 0.06-22.90) for July to September 2020; 17.2% (95% CI, 0.15-0.21) for October to December 2020; and 14.5% (95% CI, 0.09-0.21) for January to February 2021 (all P < .001) across the predefined phases. Compared with the second major outbreak, patients diagnosed in the first outbreak were more likely to be 65 years or older (974 of 1626 [60.3%] vs 564 of 1008 [56.1%]; P = .03), have at least 2 comorbidities (793 of 1626 [48.8%] vs 427 of 1008 [42.4%]; P = .001), and have advanced tumors (708 of 1626 [46.4%] vs 536 of 1008 [56.1%]; P < .001). Complications of COVID-19 were more likely to be seen (738 of 1626 [45.4%] vs 342 of 1008 [33.9%]; P < .001) and require hospitalization (969 of 1626 [59.8%] vs 418 of 1008 [42.1%]; P < .001) and anti-COVID-19 therapy (1004 of 1626 [61.7%] vs 501 of 1008 [49.7%]; P < .001) during the first major outbreak. The 14-day CFRs for the first and second major outbreaks were 25.6% (95% CI, 0.23-0.28) vs 16.2% (95% CI, 0.13-0.19; P < .001), respectively. After adjusting for country, sex, age, comorbidities, tumor stage and status, anti-COVID-19 and anticancer therapy, and COVID-19 complications, patients diagnosed in the first outbreak had an increased risk of death at 14 days (hazard ratio [HR], 1.85; 95% CI, 1.47-2.32) and 3 months (HR, 1.28; 95% CI, 1.08-1.51) compared with those diagnosed in the second outbreak., Conclusions and Relevance: The findings of this registry-based study suggest that mortality in patients with cancer diagnosed with COVID-19 has improved in Europe; this improvement may be associated with earlier diagnosis, improved management, and dynamic changes in community transmission over time.
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39. Prevalence and impact of COVID-19 sequelae on treatment and survival of patients with cancer who recovered from SARS-CoV-2 infection: evidence from the OnCovid retrospective, multicentre registry study.
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Pinato DJ, Tabernero J, Bower M, Scotti L, Patel M, Colomba E, Dolly S, Loizidou A, Chester J, Mukherjee U, Zambelli A, Dalla Pria A, Aguilar-Company J, Ottaviani D, Chowdhury A, Merry E, Salazar R, Bertuzzi A, Brunet J, Lambertini M, Tagliamento M, Pous A, Sita-Lumsden A, Srikandarajah K, Colomba J, Pommeret F, Seguí E, Generali D, Grisanti S, Pedrazzoli P, Rizzo G, Libertini M, Moss C, Evans JS, Russell B, Harbeck N, Vincenzi B, Biello F, Bertulli R, Liñan R, Rossi S, Carmona-García MC, Tondini C, Fox L, Baggi A, Fotia V, Parisi A, Porzio G, Saponara M, Cruz CA, García-Illescas D, Felip E, Roqué Lloveras A, Sharkey R, Roldán E, Reyes R, Earnshaw I, Ferrante D, Marco-Hernández J, Ruiz-Camps I, Gaidano G, Patriarca A, Bruna R, Sureda A, Martinez-Vila C, Sanchez de Torre A, Cantini L, Filetti M, Rimassa L, Chiudinelli L, Franchi M, Krengli M, Santoro A, Prat A, Van Hemelrijck M, Diamantis N, Newsom-Davis T, Gennari A, and Cortellini A
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- Adult, Aged, Aged, 80 and over, Antineoplastic Agents therapeutic use, Belgium, COVID-19 epidemiology, COVID-19 mortality, Disease Progression, Female, France, Germany, Hospitalization, Humans, Italy, Kaplan-Meier Estimate, Male, Middle Aged, Neoplasms complications, Neoplasms drug therapy, Prevalence, Registries, Retrospective Studies, Spain, United Kingdom, Post-Acute COVID-19 Syndrome, COVID-19 complications, Neoplasms epidemiology
- Abstract
Background: The medium-term and long-term impact of COVID-19 in patients with cancer is not yet known. In this study, we aimed to describe the prevalence of COVID-19 sequelae and their impact on the survival of patients with cancer. We also aimed to describe patterns of resumption and modifications of systemic anti-cancer therapy following recovery from SARS-CoV-2 infection., Methods: OnCovid is an active European registry study enrolling consecutive patients aged 18 years or older with a history of solid or haematological malignancy and who had a diagnosis of RT-PCR confirmed SARS-CoV-2 infection. For this retrospective study, patients were enrolled from 35 institutions across Belgium, France, Germany, Italy, Spain, and the UK. Patients who were diagnosed with SARS-CoV-2 infection between Feb 27, 2020, and Feb 14, 2021, and entered into the registry at the point of data lock (March 1, 2021), were eligible for analysis. The present analysis was focused on COVID-19 survivors who underwent clinical reassessment at each participating institution. We documented prevalence of COVID-19 sequelae and described factors associated with their development and their association with post-COVID-19 survival, which was defined as the interval from post-COVID-19 reassessment to the patients' death or last follow-up. We also evaluated resumption of systemic anti-cancer therapy in patients treated within 4 weeks of COVID-19 diagnosis. The OnCovid study is registered in ClinicalTrials.gov, NCT04393974., Findings: 2795 patients diagnosed with SARS-CoV-2 infection between Feb 27, 2020, and Feb 14, 2021, were entered into the study by the time of the data lock on March 1, 2021. After the exclusion of ineligible patients, the final study population consisted of 2634 patients. 1557 COVID-19 survivors underwent a formal clinical reassessment after a median of 22·1 months (IQR 8·4-57·8) from cancer diagnosis and 44 days (28-329) from COVID-19 diagnosis. 234 (15·0%) patients reported COVID-19 sequelae, including respiratory symptoms (116 [49·6%]) and residual fatigue (96 [41·0%]). Sequelae were more common in men (vs women; p=0·041), patients aged 65 years or older (vs other age groups; p=0·048), patients with two or more comorbidities (vs one or none; p=0·0006), and patients with a history of smoking (vs no smoking history; p=0·0004). Sequelae were associated with hospitalisation for COVID-19 (p<0·0001), complicated COVID-19 (p<0·0001), and COVID-19 therapy (p=0·0002). With a median post-COVID-19 follow-up of 128 days (95% CI 113-148), COVID-19 sequelae were associated with an increased risk of death (hazard ratio [HR] 1·80 [95% CI 1·18-2·75]) after adjusting for time to post-COVID-19 reassessment, sex, age, comorbidity burden, tumour characteristics, anticancer therapy, and COVID-19 severity. Among 466 patients on systemic anti-cancer therapy, 70 (15·0%) permanently discontinued therapy, and 178 (38·2%) resumed treatment with a dose or regimen adjustment. Permanent treatment discontinuations were independently associated with an increased risk of death (HR 3·53 [95% CI 1·45-8·59]), but dose or regimen adjustments were not (0·84 [0·35-2·02])., Interpretation: Sequelae post-COVID-19 affect up to 15% of patients with cancer and adversely affect survival and oncological outcomes after recovery. Adjustments to systemic anti-cancer therapy can be safely pursued in treatment-eligible patients., Funding: National Institute for Health Research Imperial Biomedical Research Centre and the Cancer Treatment and Research Trust., Competing Interests: Declaration of interests DJP reports lecture fees from ViiV Healthcare, Bayer Healthcare, Bristol Myers Squibb, Roche, Eisai, and Falk Foundation; travel expenses from Bristol Myers Squibb and Bayer Healthcare; consulting fees from Mina Therapeutics, Eisai, Roche, DaVolterra, and Astra Zeneca; and research funding (to institution) from Merck Sharp and Dohme and Bristol Myers Squibb, outside of the submitted work. MLa acted as consultant for Roche, Novartis, Lilly, and AstraZeneca, outside of the submitted work, and received speaker honoraria from Roche, Novartis, Lilly, Pfizer, Takeda, and Sandoz, outside of the submitted work. EF reports research funding to institution from Pfizer, outside of the submitted work, and travel expenses from Lilly, Novartis, Pfizer, and Esai, outside of the submitted work. TN-D reports consulting fees from Amgen, Bayer, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck Sharp and Dohme, Novartis, Otsuka, Pfizer, Roche, and Takeda, outside of the submitted work; speakers fees from AstraZeneca, Merck Sharp and Dohme, Roche, and Takeda, outside of the submitted work; and travel, accommodation, and expenses from AstraZenca, Bristol Myers Squibb, Boehringer Ingelheim, Lilly, Merck Sharp and Dohme, Otsuka, Roche, and Takeda, outside of the submitted work. JB reports consulting fees for Merck Sharp and Dohme and Astra Zeneca, outside of the submitted work. APr reports personal honoraria from Pfizer, Roche, Merck Sharp and Dohme Oncology, Eli Lilly, and Daiichi Sankyo, outside of the submitted work; travel, accommodations, and expenses by Daiichi Sankyo, outside of the submitted work; research funding (to institution) from Roche and Novartis, outside of the submitted work; and consulting fees from NanoString Technologies, Amgen, Roche, Novartis, Pfizer, and Bristol-Myers Squibb, outside of the submitted work. APar reports consulting fees from Takeda and Novartis, outside of the submitted work. MT reports travel grants from Roche, Bristol-Myers Squibb, AstraZeneca, and Takeda, outside of the submitted work; and honoraria as a medical writer from Novartis and Amgen, outside the submitted work. AG reports consulting fees from Roche, Merck Sharp and Dohme, Eli Lilly, Pierre Fabre, Eisai, and Daichii Sankyo, outside the submitted work; speakers bureau for Eisai, Novartis, Eli Lilly, Roche, Teva, Gentili, Pfizer, AstraZeneca, Celgene, and Daichii Sankyo, outside the submitted work; research funds (to institution) from Eisai, Eli Lilly, and Roche, outside the submitted work; support for attending meetings or travel from Bristol-Myers Squibb, Merck Sharp and Dohme, Novartis, and Roche, outside the submitted work; and personal research funding from Associazione Italiana per la Ricerca sul Cancro Foundation UPO aging project, outside the submitted work. GG reports personal research funding outside of the submitted work from Associazione Italiana per la Ricerca sul Cancro Foundation, outside the submitted work; consulting fees from Janssen, Abbvie, AstraZeneca, and BeiGene, outside the submitted work; and speaker fees from Janssen and Abbvie, outside the submitted work. LR reports consulting fees from Servier, Amgen, ArQule, AstraZeneca, Basilea, Bayer, Bristol Myers Squibb, Celgene, Eisai, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Lilly, Merck Sharp and Dohme, Nerviano Medical Sciences, Roche, Sanofi, and Zymeworks, outside the submitted work; lecture fees from AbbVie, Amgen, Bayer, Eisai, Gilead, Incyte, Ipsen, Lilly, Merck Serono, Roche, and Sanofi, outside the submitted work; travel expenses from Ipsen, outside the submitted work; and institutional research funding (to institution) from Agios, ARMO BioSciences, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, Merck Sharp and Dohme, Nerviano Medical Sciences, Roche, and Zymeworks, outside the submitted work. JT reports having a scientific consultancy role for Array Biopharma, AstraZeneca, Avvinity, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F Hoffmann-La Roche, Genentech, HalioDX, Hutchison MediPharma, Ikena Oncology, IQVIA, Lilly, Menarini, Merck Serono, Merus, Merck Sharp and Dohme, Mirati, Neophore, Novartis, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Tessa Therapeutics, and TheraMyc, outside of the submitted work; educational collaboration with Imedex, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education and Physicians Education Resource, outside of the submitted work; and institutional financial interest in form of financial support for clinical trials or contracted research for Amgen, Array Biopharma, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Debiopharm International, F Hoffmann-La Roche, Genentech, HalioDX, Hutchison MediPharma International, Janssen-Cilag, MedImmune, Menarini, Merck Healt, Merck Sharp and Dohme, Merus, Mirati, Novartis Farmacéutica, Pfizer, Pharma Mar, Sanofi Aventis Recherche & Développement, Servier, Taiho, Spanish Association Against Cancer Scientific Foundation, and Cancer Research UK, outside the submitted work. ACo reports consulting fees from Merck Sharp and Dohme, Bristol Myers Squibb, AstraZeneca, and Roche, outside the submitted work; and speaker fees from AstraZeneca, Merck Sharp and Dohme, Novartis, and Astellas, outside the submitted work. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
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- 2021
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40. New drugs for the treatment of metastatic colorectal cancer.
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Cherri S, Libertini M, and Zaniboni A
- Abstract
Colorectal cancer (CRC) represents one of the most frequent malignancies in terms of incidence and mortality, thus representing the third leading cause of cancer death worldwide. In the last decade, few drugs have enriched the treatment landscape of metastatic CRC and have significantly affected prognosis. Unlike other neoplasms, metastatic CRC patients who have exhausted treatment options often still maintain a good performance status. There are many challenges to increasing potential treatment options, notably a better understanding of disease biology and the mechanisms of resistance underlying cancer treatment failure. The development of new drugs for metastatic CRC certainly represents one of the most important challenges in medical oncology. This article discusses the main limitations in the development of new drugs and potential future scenarios. In particular, we addressed three questions: (1) The main limitations of targeted therapy in the treatment of metastatic CRC (mCRC); (2) New target armamentarium that could escape primary and secondary resistance and lead to more personalized mCRC therapy; and (3) Future directions., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)
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- 2021
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41. COVID-19 in breast cancer patients: a subanalysis of the OnCovid registry.
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Garrigós L, Saura C, Martinez-Vila C, Zambelli A, Bower M, Pistilli B, Lambertini M, Ottaviani D, Diamantis N, Lumsden A, Pernas S, Generali D, Seguí E, Viñas G, Felip E, Sanchez A, Rizzo G, Santoro A, Cortellini A, Perone Y, Chester J, Iglesias M, Betti M, Vincenzi B, Libertini M, Mazzoni F, Zoratto F, Berardi R, Guida A, Wuerstlein R, Loizidou A, Sharkey R, Aguilar Company J, Matas M, Saggia C, Chiudinelli L, Colomba-Blameble E, Galazi M, Mukherjee U, Van Hemelrijck M, Marin M, Strina C, Prat A, Pla H, Ciruelos EM, Bertuzzi A, Del Mastro L, Porzio G, Newsom-Davis T, Ruiz I, Delany MB, Krengli M, Fotia V, Viansone A, Chopra N, Romeo M, Salazar R, Perez I, d'Avanzo F, Franchi M, Milani M, Pommeret F, Tucci M, Pedrazzoli P, Harbeck N, Ferrante D, Pinato DJ, and Gennari A
- Abstract
Background: Cancer patients are at higher risk of COVID-19 complications and mortality than the rest of the population. Breast cancer patients seem to have better prognosis when infected by SARS-CoV-2 than other cancer patients., Methods: We report a subanalysis of the OnCovid study providing more detailed information in the breast cancer population., Results: We included 495 breast cancer patients with a SARS-CoV-2 infection. Mean age was 62.6 years; 31.5% presented more than one comorbidity. The most frequent breast cancer subtype was luminal-like ( n = 245, 49.5%) and 177 (35.8%) had metastatic disease. A total of 332 (67.1%) patients were receiving active treatment, with radical intent in 232 (47.6%) of them. Hospitalization rate was 58.2% and all-cause mortality rate was 20.3%. One hundred twenty-nine (26.1%) patients developed one COVID-19 complication, being acute respiratory failure the most common ( n = 74, 15.0%). In the multivariable analysis, age older than 70 years, presence of COVID-19 complications, and metastatic disease were factors correlated with worse outcomes, while ongoing anticancer therapy at time of COVID-19 diagnosis appeared to be a protective factor. No particular oncological treatment was related to higher risk of complications. In the context of SARS-CoV-2 infection, 73 (18.3%) patients had some kind of modification on their oncologic treatment. At the first oncological reassessment (median time: 46.9 days ± 36.7), 255 (51.6%) patients reported to be fully recovered from the infection. There were 39 patients (7.9%) with long-term SARS-CoV-2-related complications., Conclusion: In the context of COVID-19, our data confirm that breast cancer patients appear to have lower complications and mortality rate than expected in other cancer populations. Most breast cancer patients can be safely treated for their neoplasm during SARS-CoV-2 pandemic. Oncological treatment has no impact on the risk of SARS-CoV-2 complications, and, especially in the curative setting, the treatment should be modified as little as possible., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: D.J. Pinato reports personal fees from BMS (travel fees, grant to institution, and lecture fees), Eisai (consultancy, lecture fees, and occasional advisory board), H3B (consultancy and occasional advisory board), Astrazeneca (consultancy and occasional advisory board), MiNa therapeutics (consultancy), Roche (lecture fees), Viiv Healthcare (lecture fees), Bayer Healthcare (lecture fees), and Falk Foundation (lecture fees). A. Zambelli reports personal fees from Lilly (occasional advisory board and travel fees), Novartis (occasional advisory board and travel fees), Pfizer (occasional advisory board), Astrazeneca (occasional advisory board), and Roche (occasional advisory board). M. Bower reports personal fees from Gilead (lecture fees), ViiV (lecture fees), BMS (lecture fees), MSD (lecture fees), and Janssen (lecture fees). M. Lambertini reports personal fees from Roche (consultancy and travel fees), Novartis (consultancy and travel fees), Lilly (consultancy and travel fees), Astrazeneca (consultancy), Pfizer (travel fees), Sandoz (travel fees), and Takeda (travel fees). E. Felip reports personal fees from Pfizer (grant to institution) and Instituto Carlos III (research grant). A. Cortellini reports personal fees from BMS (consultancy), MSD (consultancy), Astrazeneca (consultancy and lecture fees), Roche (consultancy), Astellas (lecture fees), and Novartis (Lecture fees). F. Mazzoni reports personal fees from Roche (lecture fees), Takeda (lecture fees), MSD (lecture fees), BMS (lecture fees), Lilly (lecture fees), and Boehringer (lecture fees). M. Romeo reports personal fees from MSD (consultancy), Pfizer (travel fees), and GSK (occasional advisory board). A. Gennari reports personal fees from Astrazeneca (lecture fees), Lilly (lecture fees), Eisai (lecture fees), Pfizer (lecture fees), Novartis (lecture fees), Teva (lecture fees), and Daiichi Sankyo (lecture fees)., (© The Author(s), 2021.)
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- 2021
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42. The Role of p53 Expression in Patients with RAS/BRAF Wild-Type Metastatic Colorectal Cancer Receiving Irinotecan and Cetuximab as Later Line Treatment.
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Ziranu P, Lai E, Schirripa M, Puzzoni M, Persano M, Pretta A, Munari G, Liscia N, Pusceddu V, Loupakis F, Demurtas L, Libertini M, Mariani S, Migliari M, Dubois M, Giampieri R, Sotgiu G, Dei Tos AP, Lonardi S, Zaniboni A, Fassan M, and Scartozzi M
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- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols pharmacology, Cetuximab pharmacology, Female, Humans, Irinotecan pharmacology, Male, Middle Aged, Neoplasm Metastasis, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cetuximab therapeutic use, Colorectal Neoplasms drug therapy, Irinotecan therapeutic use, Tumor Suppressor Protein p53 metabolism
- Abstract
Background: Preclinical and clinical data indicate that p53 expression might modulate the activity of the epidermal growth factor receptor (EGFR), influencing response/resistance to anti-EGFR monoclonal antibodies. However, the association between p53 status and clinical outcome has not been clarified yet., Objective: In our study, we evaluated the role of p53 expression in patients with RAS/BRAF wild-type metastatic colorectal cancer (mCRC) receiving irinotecan/cetuximab in an exploratory and a validation cohort., Patients and Methods: p53 expression was analysed in patients with RAS/BRAF wild-type mCRC receiving second-line or third-line irinotecan/cetuximab. Survival distribution was assessed by the Kaplan-Meier method, while the log-rank test was used for survival comparison., Results: Among 120 patients with RAS/BRAF wild-type mCRC included in our analysis, 52 (59%) and 19 (59%) patients showed p53 overexpression in the exploratory and validation cohort, respectively. In the exploratory cohort, low p53 expression was correlated with better median progression-free survival (hazard ratio 0.39; p < 0.0001), median overall survival (hazard ratio: 0.23; p < 0.0001) and response rate (p < 0.0001). These results were confirmed by data of the validation cohort where we observed better median progression-free survival (hazard ratio: 0.48; p = 0.0399), median overall survival (hazard ratio: 0.26; p = 0.0027) and response rate (p =0.0007) in patients with p53 normal expression mCRC., Conclusions: In our study, p53 overexpression was associated with anti-EGFR treatment resistance in patients with RAS/BRAF WT mCRC, as confirmed in a validation cohort. Larger studies are needed to validate the role of p53 and investigate EGFR cross-talk in these patients.
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- 2021
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43. Determinants of enhanced vulnerability to coronavirus disease 2019 in UK patients with cancer: a European study.
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Pinato DJ, Scotti L, Gennari A, Colomba-Blameble E, Dolly S, Loizidou A, Chester J, Mukherjee U, Zambelli A, Aguilar-Company J, Bower M, Galazi M, Salazar R, Bertuzzi A, Brunet J, Mesia R, Sita-Lumsden A, Colomba J, Pommeret F, Seguí E, Biello F, Generali D, Grisanti S, Rizzo G, Libertini M, Moss C, Evans JS, Russell B, Wuerstlein R, Vincenzi B, Bertulli R, Ottaviani D, Liñan R, Marrari A, Carmona-García MC, Sng CCT, Tondini C, Mirallas O, Tovazzi V, Fotia V, Cruz CA, Saoudi-Gonzalez N, Felip E, R Lloveras A, Lee AJX, Newsom-Davis T, Sharkey R, Chung C, García-Illescas D, Reyes R, Sophia Wong YN, Ferrante D, Marco-Hernández J, Ruiz-Camps I, Gaidano G, Patriarca A, Sureda A, Martinez-Vila C, Sanchez de Torre A, Rimassa L, Chiudinelli L, Franchi M, Krengli M, Santoro A, Prat A, Tabernero J, V Hemelrijck M, Diamantis N, and Cortellini A
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- Aged, COVID-19 therapy, Comorbidity, Europe epidemiology, Female, Humans, Male, Middle Aged, Registries, SARS-CoV-2, United Kingdom epidemiology, COVID-19 Drug Treatment, COVID-19 epidemiology, Neoplasms complications
- Abstract
Background: Despite high contagiousness and rapid spread, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to heterogeneous outcomes across affected nations. Within Europe (EU), the United Kingdom (UK) is the most severely affected country, with a death toll in excess of 100,000 as of January 2021. We aimed to compare the national impact of coronavirus disease 2019 (COVID-19) on the risk of death in UK patients with cancer versus those in continental EU., Methods: We performed a retrospective analysis of the OnCovid study database, a European registry of patients with cancer consecutively diagnosed with COVID-19 in 27 centres from 27th February to 10th September 2020. We analysed case fatality rates and risk of death at 30 days and 6 months stratified by region of origin (UK versus EU). We compared patient characteristics at baseline including oncological and COVID-19-specific therapy across UK and EU cohorts and evaluated the association of these factors with the risk of adverse outcomes in multivariable Cox regression models., Findings: Compared with EU (n = 924), UK patients (n = 468) were characterised by higher case fatality rates (40.38% versus 26.5%, p < 0.0001) and higher risk of death at 30 days (hazard ratio [HR], 1.64 [95% confidence interval {CI}, 1.36-1.99]) and 6 months after COVID-19 diagnosis (47.64% versus 33.33%; p < 0.0001; HR, 1.59 [95% CI, 1.33-1.88]). UK patients were more often men, were of older age and have more comorbidities than EU counterparts (p < 0.01). Receipt of anticancer therapy was lower in UK than in EU patients (p < 0.001). Despite equal proportions of complicated COVID-19, rates of intensive care admission and use of mechanical ventilation, UK patients with cancer were less likely to receive anti-COVID-19 therapies including corticosteroids, antivirals and interleukin-6 antagonists (p < 0.0001). Multivariable analyses adjusted for imbalanced prognostic factors confirmed the UK cohort to be characterised by worse risk of death at 30 days and 6 months, independent of the patient's age, gender, tumour stage and status; number of comorbidities; COVID-19 severity and receipt of anticancer and anti-COVID-19 therapy. Rates of permanent cessation of anticancer therapy after COVID-19 were similar in the UK and EU cohorts., Interpretation: UK patients with cancer have been more severely impacted by the unfolding of the COVID-19 pandemic despite societal risk mitigation factors and rapid deferral of anticancer therapy. The increased frailty of UK patients with cancer highlights high-risk groups that should be prioritised for anti-SARS-CoV-2 vaccination. Continued evaluation of long-term outcomes is warranted., Competing Interests: Conflict of interest statement D.J.P. received lecture fees from ViiV Healthcare and Bayer Healthcare, travel expenses from BMS and Bayer Healthcare; consulting fees for MiNA Therapeutics, EISAI, Roche and AstraZeneca and research funding (to the institution) from MSD and BMS. A.P. has declared personal honoraria from Pfizer, Roche, MSD Oncology, Eli Lilly and Daiichi Sankyo; travel, accommodations and expenses paid by Daiichi Sankyo; research funding from Roche and Novartis and a consulting/advisory role for NanoString Technologies, Amgen, Roche, Novartis, Pfizer and Bristol Myers Squibb. T.N-D. has declared a consulting/advisory role for Amgen, Bayer, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Otsuka, Pfizer, Roche and Takeda; speaker fees from AstraZeneca, MSD, Roche, Takeda and travel, accommodations and expenses paid by AstraZenca, BMS, Boehringer Ingelheim, Lilly, MSD, Otsuka, Roche and Takeda. J.B. has declared a consulting/advisory role for MSD and AstraZeneca. PPS has declared a consulting/advisory role for Sanofi and AbbVie. A.P. has declared a consulting/advisory role for Takeda and Sanofi. MP has declared a consulting/advisory role for Gilead and Bayer. A.G. has declared a consulting/advisory role for Roche, MSD, Eli Lilly, Pierre Fabre, EISAI and Daiichi Sankyo; is on the speaker's bureau for Eisai, Novartis, Eli Lilly, Roche, Teva, Gentili, Pfizer, AstraZeneca, Celgene and Daiichi Sankyo and declared research funds from EISAI, Eli Lilly and Roche. C.M.-V. has received travel grants and other honoraria from BMS, MSD, Novartis and Roche. L.R. received consulting fees from Amgen, ArQule, AstraZeneca, Basilea, Bayer, BMS, Celgene, Eisai, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Lilly, MSD, Nerviano Medical Sciences, Roche, Sanofi and Zymeworks; lecture fees from AbbVie, Amgen, Bayer, Eisai, Gilead, Incyte, Ipsen, Lilly, Merck Serono, Roche and Sanofi; travel expenses from Ipsen and institutional research funding from Agios, ARMO BioSciences, AstraZeneca, BeiGene, Eisai, Exelixis, FibroGen, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche and Zymeworks. J.T. reports personal financial interest in form of a scientific consultancy role for Array BioPharma, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd., Genentech, Inc., HalioDX SAS, Ikena Oncology, IQVIA, Imedex, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, NeoPhore, Novartis, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Tessa Therapeutics and TheraMyc. A.C. received consulting fees from MSD, BMS, AstraZeneca, Roche and speakers' fee from AstraZeneca, MSD, Novartis and Astellas. All the remaining authors have declared no conflicts of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
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- 2021
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44. Systemic pro-inflammatory response identifies patients with cancer with adverse outcomes from SARS-CoV-2 infection: the OnCovid Inflammatory Score.
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Dettorre GM, Dolly S, Loizidou A, Chester J, Jackson A, Mukherjee U, Zambelli A, Aguilar-Company J, Bower M, Sng CCT, Salazar R, Bertuzzi A, Brunet J, Mesia R, Sita-Lumsden A, Seguí E, Biello F, Generali D, Grisanti S, Seeva P, Rizzo G, Libertini M, Maconi A, Moss C, Russell B, Harbeck N, Vincenzi B, Bertulli R, Ottaviani D, Liñan R, Marrari A, Carmona-García MC, Chopra N, Tondini CA, Mirallas O, Tovazzi V, Fotia V, Cruz CA, Saoudi-Gonzalez N, Felip E, Roqué A, Lee AJX, Newsom-Davis T, García-Illescas D, Reyes R, Wong YNS, Ferrante D, Scotti L, Marco-Hernández J, Ruiz-Camps I, Patriarca A, Rimassa L, Chiudinelli L, Franchi M, Santoro A, Prat A, Gennari A, Van Hemelrijck M, Tabernero J, Diamantis N, and Pinato DJ
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- Adult, Aged, Aged, 80 and over, Blood Cell Count, COVID-19 complications, COVID-19 mortality, COVID-19 Testing, Comorbidity, Female, Humans, Male, Middle Aged, Multivariate Analysis, Neoplasms epidemiology, Prognosis, Systemic Inflammatory Response Syndrome virology, Young Adult, Neoplasms virology, Systemic Inflammatory Response Syndrome etiology, COVID-19 Drug Treatment
- Abstract
Background: Patients with cancer are particularly susceptible to SARS-CoV-2 infection. The systemic inflammatory response is a pathogenic mechanism shared by cancer progression and COVID-19. We investigated systemic inflammation as a driver of severity and mortality from COVID-19, evaluating the prognostic role of commonly used inflammatory indices in SARS-CoV-2-infected patients with cancer accrued to the OnCovid study., Methods: In a multicenter cohort of SARS-CoV-2-infected patients with cancer in Europe, we evaluated dynamic changes in neutrophil:lymphocyte ratio (NLR); platelet:lymphocyte ratio (PLR); Prognostic Nutritional Index (PNI), renamed the OnCovid Inflammatory Score (OIS); modified Glasgow Prognostic Score (mGPS); and Prognostic Index (PI) in relation to oncological and COVID-19 infection features, testing their prognostic potential in independent training (n=529) and validation (n=542) sets., Results: We evaluated 1071 eligible patients, of which 625 (58.3%) were men, and 420 were patients with malignancy in advanced stage (39.2%), most commonly genitourinary (n=216, 20.2%). 844 (78.8%) had ≥1 comorbidity and 754 (70.4%) had ≥1 COVID-19 complication. NLR, OIS, and mGPS worsened at COVID-19 diagnosis compared with pre-COVID-19 measurement (p<0.01), recovering in survivors to pre-COVID-19 levels. Patients in poorer risk categories for each index except the PLR exhibited higher mortality rates (p<0.001) and shorter median overall survival in the training and validation sets (p<0.01). Multivariable analyses revealed the OIS to be most independently predictive of survival (validation set HR 2.48, 95% CI 1.47 to 4.20, p=0.001; adjusted concordance index score 0.611)., Conclusions: Systemic inflammation is a validated prognostic domain in SARS-CoV-2-infected patients with cancer and can be used as a bedside predictor of adverse outcome. Lymphocytopenia and hypoalbuminemia as computed by the OIS are independently predictive of severe COVID-19, supporting their use for risk stratification. Reversal of the COVID-19-induced proinflammatory state is a putative therapeutic strategy in patients with cancer., Competing Interests: Competing interests: DJP received lecture fees from ViiV Healthcare and Bayer Healthcare and travel expenses from BMS and Bayer Healthcare; consulting fees for Mina Therapeutics, EISAI, Roche, and Astra Zeneca; research funding (to institution) from MSD and BMS. AP has declared personal honoraria from Pfizer, Novartis, Roche, MSD Oncology, Eli Lilly, and Daiichi Sankyo; travel, accommodations, and expenses paid by Daiichi Sankyo; research funding from Roche and Novartis; and consulting/advisory role for NanoString Technologies, Amgen, Roche, Novartis, Pfizer and Bristol-Myers Squibb. TND has declared consulting/advisory role for Amgen, Bayer, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Otsuka, Pfizer, Roche, and Takeda; speakers fees from AstraZeneca, MSD, Roche, Takeda; and travel, accommodations and expenses paid by AstraZenca, BMS, Boehringer Ingelheim, Lilly, MSD, Otsuka, Roche, and Takeda. JB has declared consulting/advisory role for MSD and Astra Zeneca. PPS has declared consulting/advisory role for Sanofi and Abbvie. AP has declared consulting/advisory role for Takeda and Sanofi. MP has declared consulting/advisory role for Gilead and Bayer. AG has declared consulting/advisory role for Roche, MSD, Eli Lilly, Pierre Fabre, EISAI, and Daichii Sankyo; speakers bureau for Eisai, Novartis, Eli Lilly, Roche, Teva, Gentili, Pfizer, Astra Zeneca, Celgene, and Daichii Sankyo; research funds: EISAI, Eli Lilly, and Roche. LR reports receiving consulting fees from Amgen, ArQule, AstraZeneca, Basilea, Bayer, Celgene, Eisai, Exelixis, Hengrui, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, and Sanofi; lectures fees from AbbVie, Amgen, Eisai, Gilead, Incyte, Ipsen, Lilly, Roche, and Sanofi; travel fees from Ipsen; and institutional research funding from Agios, ARMO BioSciences, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, MSD, and Roche. All remaining authors have declared no conflicts of interest., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)
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- 2021
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45. Gynecological Sarcomas: Molecular Characteristics, Behavior, and Histology-Driven Therapy.
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Libertini M, Hallin M, Thway K, Noujaim J, Benson C, van der Graaf W, and Jones RL
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- Female, Genital Neoplasms, Female mortality, Genital Neoplasms, Female pathology, Genital Neoplasms, Female therapy, Humans, Immunohistochemistry, Molecular Diagnostic Techniques, Neoplasm Grading, Ovary pathology, Progression-Free Survival, Sarcoma mortality, Sarcoma pathology, Sarcoma therapy, Uterus pathology, Vagina pathology, Vulva pathology, Biomarkers, Tumor analysis, Chemoradiotherapy, Adjuvant methods, Genital Neoplasms, Female diagnosis, Gynecologic Surgical Procedures methods, Sarcoma diagnosis
- Abstract
Gynecological sarcomas represent 3% to 4% of all gynecological malignancies and 13% of all sarcomas. The uterus is the most frequent primary site (83%); less frequently sarcomas are diagnosed originating from the ovary (8%), vulva and vagina (5%), and other gynecologic organs (2%). As the classification of gynecologic sarcomas continues to diversify, so does the management. Accurate histopathologic diagnosis, utilizing appropriate ancillary immunohistochemical and molecular analysis, could lead to a more personalized approach. However, there are subtypes that require further definition, with regard to putative predictive markers and optimal management. The aim of this review is to highlight the importance of accurate diagnosis and classification of gynecologic sarcoma subtypes by the surgical pathologist in order to provide more tailored systemic treatment, and to highlight the increasing importance of close collaboration between the pathologist and the oncologist.
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- 2021
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46. Cutaneous Adnexal Carcinoma with Apocrine Differentiation: A Challenging Diagnosis and Personalized Treatment with mTOR Inhibitor in a Very Rare Disease.
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Libertini M, Oneda E, Di Biasi B, Savelli G, and Zaniboni A
- Abstract
Cutaneous adnexal carcinoma with apocrine differentiation is a rare neoplasm arising from cutaneous adnexa, especially of the head and neck and trunk region. Because of its rarity, the diagnosis is challenging and often impossible to distinguish from metastatic cutaneous adenocarcinoma of the breast. The standard of care remains surgery for resectable disease. To date, univocal guidelines for metastatic disease are lacking, particularly regarding systemic therapy. We report a clinical case of a patient diagnosed with cutaneous adnexal adenocarcinoma with apocrine differentiation of the left axilla with lymph node and bone metastasis. We started with carboplatin and paclitaxel chemotherapy regimen, with good response. After progression, we performed a next-generation sequencing analysis (by the Foundation One CDx test) to identify genomic alteration in cancer-related genes. We found PIK3CA and KRAS mutations. Due to this result, the patient started a second-line treatment with a personalized therapy including an mTOR inhibitor, everolimus, and, to date, he is still under treatment. To our knowledge, this is the first case of a patient responding both to chemotherapy and to a personalized treatment with an mTOR inhibitor. It is important to support the value of genomic screening in this rare neoplasm., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 by S. Karger AG, Basel.)
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- 2020
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47. Clinical portrait of the SARS-CoV-2 epidemic in European cancer patients.
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Pinato DJ, Zambelli A, Aguilar-Company J, Bower M, Sng C, Salazar R, Bertuzzi A, Brunet J, Mesia R, Segui E, Biello F, Generali D, Grisanti S, Rizzo G, Libertini M, Maconi A, Harbeck N, Vincenzi B, Bertulli R, Ottaviani D, Carbo A, Bruna R, Benafif S, Marrari A, Wuerstlein R, Carmona-Garcia MC, Chopra N, Tondini C, Mirallas O, Tovazzi V, Betti M, Provenzano S, Fotia V, Cruz CA, Dalla Pria A, D'Avanzo F, Evans JS, Saoudi-Gonzalez N, Felip E, Galazi M, Garcia-Fructuoso I, Lee AJX, Newsom-Davis T, Patriarca A, Garcia-Illescas D, Reyes R, Dileo P, Sharkey R, Wong YNS, Ferrante D, Marco-Hernandez J, Sureda A, Maluquer C, Ruiz-Camps I, Gaidano G, Rimassa L, Chiudinelli L, Izuzquiza M, Cabirta A, Franchi M, Santoro A, Prat A, Tabernero J, and Gennari A
- Abstract
The SARS-Cov-2 pandemic significantly impacted on oncology practice across the globe. There is uncertainty as to the contribution of patients' demographics and oncological features on severity and mortality from Covid-19 and little guidance as to the role of anti-cancer and anti-Covid-19 therapy in this population. In a multi-center study of 890 cancer patients with confirmed Covid-19 we demonstrated a worsening gradient of mortality from breast cancer to haematological malignancies and showed that male gender, older age, and number of co-morbidities identifies a subset of patients with significantly worse mortality rates from Covid-19. Provision of chemotherapy, targeted therapy and immunotherapy did not worsen mortality. Exposure to antimalarials was associated with improved mortality rates independent of baseline prognostic factors. This study highlights the clinical utility of demographic factors for individualized risk-stratification of patients and support further research into emerging anti-Covid-19 therapeutics in SARS-Cov-2 infected cancer patients., (Copyright ©2020, American Association for Cancer Research.)
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- 2020
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48. From CENTRAL to SENTRAL (SErum aNgiogenesis cenTRAL): Circulating Predictive Biomarkers to Anti-VEGFR Therapy.
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Giampieri R, Ziranu P, Daniele B, Zizzi A, Ferrari D, Lonardi S, Zaniboni A, Cavanna L, Rosati G, Casagrande M, Pella N, Demurtas L, Zampino MG, Sozzi P, Pusceddu V, Germano D, Lai E, Zagonel V, Codecà C, Libertini M, Puzzoni M, Labianca R, Cascinu S, and Scartozzi M
- Abstract
Background: In the last decade, a series of analyses failed to identify predictive biomarkers of resistance/susceptibility for anti-angiogenic drugs in metastatic colorectal cancer (mCRC). We conducted an exploratory preplanned analysis of serum pro-angiogenic factors (SErum aNgiogenesis-cenTRAL) in 72 mCRC patients enrolled in the phase II CENTRAL (ColorEctalavastiNTRiAlLdh) trial, with the aim to identify potential predictive factors for sensitivity/resistance to first line folinic acid-fluorouracil-irinotecan regimen (FOLFIRI) plus bevacizumab., Methods: First-line FOLFIRI/bevacizumab patients were prospectively assessed for the following circulating pro-angiogenic factors, evaluated with ELISA (enzyme-linked immunosorbent assay)-based technique at baseline and at every cycle: Vascular endothelial growth factor A (VEGF-A), hepatocyte growth factor (HGF), stromal derived factor-1 (SDF-1), placental derived growth factor (PlGF), fibroblast growth factor-2 (FGF-2), monocyte chemotactic protein-3 (MCP-3), interleukin-8 (IL-8)., Results: Changes in circulating FGF-2 levels among different blood samples seemed to correlate with clinical outcome. Patients who experienced an increase in FGF-2 levels at the second cycle of chemotherapy compared to baseline, had a median Progression Free Survival (mPFS) of 12.85 vs. 7.57 months (Hazard Ratio-HR: 0.73, 95% Confidence Interval-CI: 0.43-1.27, p = 0.23). Similar results were seen when comparing FGF-2 concentrations between baseline and eight-week time point (mPFS 12.98 vs. 8.00 months, HR: 0.78, 95% CI: 0.46-1.33, p = 0.35)., Conclusions: Our pre-planned, prospective analysis suggests that circulating FGF-2 levels' early increase could be used as a marker to identify patients who are more likely to gain benefit from FOLFIRI/bevacizumab first-line therapy.
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- 2020
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49. Impact of age and gender on the safety and efficacy of chemotherapy plus bevacizumab in metastatic colorectal cancer: a pooled analysis of TRIBE and TRIBE2 studies.
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Marmorino F, Rossini D, Lonardi S, Moretto R, Zucchelli G, Aprile G, Dell'Aquila E, Ratti M, Bergamo F, Masi G, Urbano F, Ronzoni M, Libertini M, Borelli B, Randon G, Buonadonna A, Allegrini G, Pella N, Ricci V, Boccaccino A, Latiano TP, Cordio S, Passardi A, Tamburini E, Boni L, Falcone A, and Cremolini C
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- Age Factors, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bevacizumab adverse effects, Camptothecin administration & dosage, Camptothecin adverse effects, Colorectal Neoplasms epidemiology, Colorectal Neoplasms pathology, Female, Fluorouracil administration & dosage, Fluorouracil adverse effects, Humans, Kaplan-Meier Estimate, Leucovorin administration & dosage, Leucovorin adverse effects, Male, Middle Aged, Nausea chemically induced, Nausea pathology, Neoplasm Metastasis, Organoplatinum Compounds administration & dosage, Organoplatinum Compounds adverse effects, Progression-Free Survival, Sex Characteristics, Treatment Outcome, Vomiting chemically induced, Vomiting pathology, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Bevacizumab administration & dosage, Camptothecin analogs & derivatives, Colorectal Neoplasms drug therapy
- Abstract
Background: The phase III TRIBE and TRIBE2 studies randomized metastatic colorectal cancer patients to first-line FOLFOXIRI/bevacizumab or a doublet (FOLFIRI or FOLFOX)/bevacizumab. The studies demonstrated a significant benefit from the triplet at the price of an increased incidence of chemotherapy-related adverse events (AEs). In both trials, males and females aged between 18 and 70 years with ECOG PS ≤2 and between 71 and 75 years with ECOG PS = 0 were eligible. We investigated the effect of FOLFOXIRI/bevacizumab versus doublets/bevacizumab according to age and gender., Patients and Methods: Subgroup analyses according to age (<70 versus 70-75 years) and gender were carried out for overall response rate (ORR), progression-free survival (PFS), and AE rates., Results: Of 1187 patients, 1005 (85%) were aged <70 years and 182 (15%) 70-75 years; 693 (58%) were males and 494 (42%) females. There was no evidence of interaction between age or gender and the benefit provided by the intensification of the upfront chemotherapy in terms of ORR and PFS, or the increased risk of experiencing G3/4 AEs. Elderly patients and females experienced higher rates of overall G3/4 AEs (73% versus 60%, P < 0.01 and 69% versus 57%, P < 0.01, respectively). Notably, in the FOLFOXIRI/bevacizumab subgroup, G3/4 diarrhea and febrile neutropenia occurred in 27% and 16% of elderly patients, respectively, while females reported high incidences of any grade nausea (67%) and vomiting (50%)., Conclusions: The improvements in terms of ORR and PFS of FOLFOXIRI/bevacizumab versus doublets/bevacizumab are independent of gender and age, with a similar relative increase in AEs among elderly patients and females. Initial dose reductions and possibly primary G-CSF prophylaxis should be recommended for patients between 70 and 75 years old treated with FOLFOXIRI/bevacizumab, and a careful management of antiemetic prophylaxis should be considered among females., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2019
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50. Timing of Adjuvant Chemotherapy and Survival in Colorectal, Gastric, and Pancreatic Cancer. A Systematic Review and Meta-Analysis.
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Petrelli F, Zaniboni A, Ghidini A, Ghidini M, Turati L, Pizzo C, Ratti M, Libertini M, and Tomasello G
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(1) Background: The optimal timing of adjuvant chemotherapy (CT) in gastrointestinal malignancies is still a matter of debate. For colorectal cancer, it is recommended to start post-operative treatment within eight weeks. The objective of this study was to assess the clinical effects of starting adjuvant CT within or after 6-8 weeks post-surgery in colorectal, gastric, and pancreatic cancer. (2) Methods: MEDLINE, EMBASE, and the Cochrane Library were searched in December 2018. Publications comparing the outcomes of patients treated with adjuvant CT administered before (early) or after (delayed) 6-8 weeks post-surgery for colorectal, gastric, and pancreatic cancer were identified. The primary endpoint was overall survival (OS). (3) Results: Out of 8752 publications identified, 34 comparative studies assessing a total of 141,853 patients were included. Meta-analysis indicated a statistically significant increased risk of death with delayed CT (>6-8 weeks post-surgery) in colorectal cancer (hazard ratio (HR) = 1.27, 95% confidence interval (CI) 1.21-1.33; p <0.001). Similarly, for gastric cancer, delaying adjuvant CT was associated with inferior overall survival (HR = 1.2, 95% CI 1.04-1.38; p = 0.01). Conversely, the benefit of earlier CT was not evident in pancreatic cancer (HR = 1, 95% CI 1-1.01; p = 0.37). Conclusions: Starting adjuvant CT within 6-8 weeks post-surgery is associated with a significant survival benefit for colorectal and gastric cancer, but not for pancreatic cancer., Competing Interests: The authors declare no conflict of interest.
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- 2019
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