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Del Conte G.,San Raffaele Scientific Institute | Sessa C.,San Raffaele Scientific Institute | Sessa C.,Oncology Institute of Southern Switzerland | Von Moos R.,Kantonsspital Graubu Nden | And 8 more authors.
British Journal of Cancer | Year: 2014

Background:Olaparib, an oral PARP inhibitor, has shown antitumour activity as monotherapy in patients with germline BRCA1/2 (gBRCA)-mutated breast and ovarian cancer. This study evaluated olaparib capsules in combination with liposomal doxorubicin (PLD) in patients with advanced solid tumours (NCT00819221).Methods:Patients received 28-day cycles of olaparib, continuously (days 1-28) or intermittently (days 1-7), plus PLD (40 mg m-2, day 1); seven olaparib dose cohorts (50-400 mg bid) were explored to determine the recommended dose. Assessments included safety, pharmacokinetics, pharmacodynamics and preliminary efficacy (objective response rate (ORR)).Results:Of 44 patients treated (ovarian, n=28; breast, n=13; other/unknown, n=3), two experienced dose-limiting toxicities (grade 3 stomatitis and fatal pneumonia/pneumonitis (200 mg per 28-day cycle); grade 4 thrombocytopenia (400 mg per 7-day cycle)). The maximum tolerated dose was not reached using continuous olaparib 400 mg bid plus PLD. Grade ≥3 and serious AEs were reported for 27 (61%) and 12 (27%) patients, respectively. No major pharmacokinetic interference was observed between olaparib and PLD. The ORR was 33% (n=14 out of 42; complete response, n=3). A total of 13 responders had ovarian cancer: 10 were platinum-sensitive, 11 had a gBRCA mutation.Conclusions:Continuous/intermittent olaparib (up to 400 mg bid) combined with PLD (40 mg m-2) was generally tolerated and showed evidence of antitumour activity in ovarian cancer. © 2014 Cancer Research UK. All rights reserved. Source

Kusamura S.,Peritoneal Surface Malignancy Program | Torres Mesa P.A.,Peritoneal Surface Malignancy Program | Torres Mesa P.A.,Surface Oncology | Cabras A.,Fondazione Istituto Nazionale Dei Tumori di Milan | And 2 more authors.
Annals of Surgical Oncology | Year: 2016

Background: We conducted a prognostic analysis of preoperative parameters and Ki-67 determination to develop selection criteria for cytoreductive surgery (CRS) and HIPEC in patients with diffuse malignant peritoneal mesothelioma (DMPM). Methods: DMPM patients treated with CRS and HIPEC at NCI of Milan participated in this study. Multivariate analysis was conducted using Cox proportional hazard model and conditional inference tree method to select independent predictors of overall survival (OS) from the followings pre-cytoreduction parameters: age, sex, ECOG performance status, Charlson comorbidity index, previous systemic chemotherapy, CA-125, histological subtype (epithelioid vs. biphasic/sarcomatoid), Ki-67 (determined with immunohistochemistry), and peritoneal cancer index (PCI). Results: A total of 117 patients (male/female: 67/50) with median age of 60.5 (range 22–75) years were included. Eighty-three patients had ECOG performance status = 0, median Charlson comorbidity index was 4 (range 2–9), and 102 cases had epithelioid subtype. Median Ki-67 was 5 % (range 1–60). Ninety-four (80.3 %) cases were optimally cytoreduced. The Cox analysis identified Ki-67, PCI, and histological subtype as independent prognosticators of OS. Conditional inference tree method identified three prognostic subsets: (I) Ki-67 ≤ 9 %; (II) Ki-67 > 9 % and PCI ≤ 17; and (III) Ki-67 > 9 % and PCI > 17. The median OS for subsets I, II, and III were, 86.6, 63.2, and 10.3 months, respectively. Conclusions: Ki-67 is a powerful prognosticator that allows, along with PCI, and histological subtype, a good prediction of OS in patients with DMPM. Patients with Ki-67 > 9 % and PCI > 17 are unlikely to benefit from the procedure and should be considered for other treatment protocols. © 2015, Society of Surgical Oncology. Source

Deraco M.,Peritoneal Surface Malignancy Program | Cabras A.,Fondazione Istituto Nazionale Dei Tumori di Milan | Baratti D.,Peritoneal Surface Malignancy Program | Kusamura S.,Peritoneal Surface Malignancy Program
Annals of Surgical Oncology | Year: 2015

Purpose: Immunohistochemistry and tissue microarray (TMA) were used to perform a prognostic analysis of markers related to cell proliferation in diffuse malignant peritoneal mesothelioma (DMPM). Methods: Clinicopathologic data were extracted from a prospectively collected database containing cases of peritoneal mesothelioma treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the National Cancer Institute of Milan from 1995 to 2013. Eighty-one DMPM patients were recruited and their tissue samples were used to construct TMAs. We evaluated the immunoexpressions of markers related to cell proliferation—topoisomerase IIα, minichromosome maintenance protein 7 (MCM7), and Ki-67—and then conducted a multivariate Cox model to identify the predictors of overall survival (OS) and progression-free survival (PFS) among the following parameters: age, sex, Eastern Cooperative Oncology Group (ECOG) performance status, baseline serum albumin, Charlson Comorbidity Index, previous systemic chemotherapy, histological subtype (epithelioid vs. biphasic/sarcomatoid), peritoneal cancer index, completeness of cytoreduction (CC), and proliferative biological markers. Results: The rates of high/intermediate immunoreactivity were 95 % for topoisomerase IIα and 90 % for MCM7, and the median Ki-67 labeling index was 5 %. The independent predictors of OS were baseline serum albumin >3.5 g/dl, CC, and Ki-67 >5 %, whereas those for PFS were an ECOG performance status of 0, baseline serum albumin >3.5 g/dl, Charlson Comorbidity Index >3, previous systemic chemotherapy, morbidity G3–5, and Ki-67 >5 %. The remaining biological markers were not associated with outcome. Conclusions: Ki-67 was found to be a new powerful determinant of outcome. Patients with a Ki-67 labeling index >5 % carry a very poor prognosis and do not benefit from the combined procedure. Further studies should be conducted to confirm the present data. © 2015, Society of Surgical Oncology. Source

Seregni E.,Fondazione Istituto Nazionale Dei Tumori di Milan
Tumori | Year: 2010

Pulmonary and digestive neuroendocrine tumors (NETs) are a group of neoplasms whose incidence and prevalence has been constantly increasing over the last years thanks to the significant improvements in instrumental diagnostic techniques. Because NETs are extremely heterogeneous a correct histopathological diagnosis is essential for appropriate treatment. More specifically, the histopathological diagnosis of NETs can be regarded as a multistep: identification of the neuroendocrine nature of the neoplasm, determination of tumor grading; identification of unknown primary. Laboratory biomarkers for the study of gastroenteropancreatic neuroendocrine tumors include both specific markers and non-specific or general markers. At the moment, chromogranin A is the best available and most frequently used biomarker for the diagnosis of NETs, offering the highest overall sensitivity. CgA has also demonstrated some utility in the assessment of response to treatment and as indicator of tumor recurrence. Free full text available at www.tumorionline.it. Source

Locatelli P.,Polytechnic of Milan | Montefusco V.,Fondazione Istituto Nazionale Dei Tumori di Milan | Sini E.,Istituto Clinico Humanitas | Restifo N.,Polytechnic of Milan | And 2 more authors.
Studies in Health Technology and Informatics | Year: 2013

The volume and the complexity of clinical and administrative information make Information and Communication Technologies (ICTs) essential for running and innovating healthcare. This paper tells about a project aimed to design, develop and implement a set of organizational models, acknowledged procedures and ICT tools (Mobile & Wireless solutions and Automatic Identification and Data Capture technologies) to improve actual support, safety, reliability and traceability of a specific therapy management (stem cells). The value of the project is to design a solution based on mobile and identification technology in tight collaboration with physicians and actors involved in the process to ensure usability and effectivenes in process management. © 2013 IMIA and IOS Press. Source

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