Reni M.,San Raffaele Scientific Institute |
Cereda S.,San Raffaele Scientific Institute |
Milella M.,Regina Elena Cancer Institute |
Novarino A.,Onco Hematological Subalpine Center |
And 11 more authors.
European Journal of Cancer | Year: 2013
Background: New strategies to prolong disease control warrant investigation in patients with metastatic pancreatic adenocarcinoma. This open-label, randomised, multi-centre phase II trial explored the role of maintenance sunitinib after first-line chemotherapy in this setting. Methods: Patients with pathologic diagnosis of metastatic pancreatic adenocarcinoma, performance status >50%, no progression after 6 months of chemotherapy were centrally randomised by an independent contract research organisation, which was also responsible for data collection and monitoring, to observation (arm A) or sunitinib at 37.5 mg daily until progression or a maximum of 6 months (arm B). The primary outcome measure was the probability of being progression-free at 6 months (PFS-6) from randomisation. Assuming P0 = 10%; P1 = 30%, α.10; β.10, the target accrual was 26 patients per arm. Results: 28 per arm were randomised. One arm B patient had kidney cancer and was excluded. Sunitinib was given for a median of 91 days (7-186). Main grade 3-4 toxicity was thrombocytopenia, neutropenia and hand-foot syndrome (12%), diarrhoea 8%. In arm A versus B, PFS-6 was 3.6% (95% confidence interval (CI): 0-10.6%) and 22.2% (95% CI: 6.2-38.2%; P < 0.01); 2y overall survival was 7.1% (95% CI: 0-16.8%) and 22.9% (95% CI: 5.8-40.0%; P = 0.11), stable disease 21.4% and 51.9% (P = 0.02). Conclusion: This is the first randomised trial on maintenance therapy in metastatic pancreatic adenocarcinoma. The primary end-point was fulfilled and 2y overall survival was remarkably high, suggesting that maintenance sunitinib is promising and should be further explored in this patient population. © 2013 Elsevier Ltd. All rights reserved. Source
Totaro P.,IRCCS Foundation San Matteo |
Morganti S.,IRCCS FoundationPoliclinico San Matteo |
Ngo Yon C.L.,IRCCS Foundation San Matteo |
Dore R.,University of Pavia |
And 4 more authors.
Journal of Heart Valve Disease | Year: 2012
Background and aim of the study: Aortic valve-sparing (AVS) procedures have been introduced to treat ascending aorta dilatation and aortic valve insufficiency in the presence of preserved native aortic valve leaflets. Although the surgical technique has been standardized, the choice of best type and size of Dacron graft to be used remains a matter of debate. Herein are presented preliminary results based on a patient-specific finite element model aimed at optimizing the Dacron prosthesis size and shape. Previously, finite element analysis (FEA) has been applied to investigate medical problems and, in particular, to better evaluate the pathophysiology of the aortic root. To date, however, such methodology has not been applied to the patient-specific evaluation of AVS postoperative results. Methods: The framework of the FEA study included four steps: (i) the creation of a mathematic model of the patient's aortic root; (ii) the creation of a model for two different Dacron grafts (the standard straight graft and a Valsalva graft), with sizes of each type ranging from 24 to 30 mm; (iii) a virtual computerbased simulation of the AVS procedure, using each graft; and (iv) a virtual computer-based simulation of the diastolic closure of the repaired valve and an evaluation of post-implant physiology, based on three parameters: the height of coaptation ratio (HCR); the length of coaptation ratio (LCR); and the distance between the central point of coaptation and the ideal geometrical centre (DC). Results: The simulation results of post-implant performance of the aortic valve revealed that both HCR and LCR were decreased as the graft size was increased, but no significant differences were identified between two types of graft. In contrast, the Valsalva graft, when compared to the standard straight graft, led to a significant reduction in DC. The results in terms of HCR, LCR and DC recommended unequivocally, for the specific case under investigation, that a 30 mm straight graft and a 28 mm Valsalva graft would ensure the most physiological valve behavior for the patient under investigation. Conclusion: In evaluating the potential of a preoperative prediction of the optimal graft size, using FEA, the virtual simulation of the AVS procedure proved to be feasible and useful in predicting the postoperative physiology of the aortic root. In particular, this finite element model might have a clinical impact as may be used to optimize the surgeon's choice of prosthesis size. © Copyright by ICR Publishers 2012. Source