Institute of Cancer Research and Treatment

Candiolo, Italy

Institute of Cancer Research and Treatment

Candiolo, Italy
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Ascierto P.A.,Instituto Nazionale Tumori Fondazione G Pascale | Simeone E.,Instituto Nazionale Tumori Fondazione G Pascale | Sileni V.C.,Veneto Institute of Oncology IOV IRCCS | Pigozzo J.,Veneto Institute of Oncology IOV IRCCS | And 17 more authors.
Journal of Translational Medicine | Year: 2014

Background: Ipilimumab improves survival in patients with advanced melanoma. The activity and safety of ipilimumab outside of a clinical trial was assessed in an expanded access programme (EAP).Methods: Ipilimumab was available upon physician request for patients aged 16 or over with pretreated stage III (unresectable)/IV melanoma, for whom no other therapeutic option was available. Patients received ipilimumab 3 mg/kg every 3 weeks for four doses. Patients with stable disease or an objective response to ipilimumab were eligible for retreatment upon disease progression. Tumour assessments were conducted at baseline and week 12. Patients were monitored for adverse events (AEs) within 3 to 4 days of each scheduled visit.Results: Of 855 patients participating in the EAP in Italy, 833 were evaluable for response. Of these, 13% had an objective immune response, and the immune-related disease control rate was 34%. Median progression-free survival and overall survival were 3.7 and 7.2 months, respectively. Efficacy was independent of BRAF and NRAS mutational status. Overall, 33% of patients reported an immune-related AE (irAE). The frequency of irAEs was not associated with response to ipilimumab.Conclusions: Outside of a clinical trial setting, ipilimumab is a feasible treatment option in patients with pretreated metastatic melanoma, regardless of BRAF and NRAS mutational status. Data from this large cohort of patients support clinical trial evidence that ipilimumab can induce durable disease control and long-term survival in patients who have failed to respond to prior treatment. © 2014 Ascierto et al.; licensee BioMed Central Ltd.


Rahbari N.N.,University of Heidelberg | Garden O.J.,University of Edinburgh | Padbury R.,Flinders Medical Center | Maddern G.,University of Adelaide | And 21 more authors.
HPB | Year: 2011

Background: A standardized definition of post-hepatectomy haemorrhage (PHH) has not yet been established. Methods: An international study group of hepatobiliary surgeons from high-volume centres was convened and a definition of PHH was developed together with a grading of severity considering the impact on patients' clinical management. Results: The definition of PHH varies strongly within the hepatic surgery literature. PHH is defined as a drop in haemoglobin level >3 g/dl post-operatively compared with the post-operative baseline level and/or any post-operative transfusion of packed red blood cells (PRBC) for a falling haemoglobin and/or the need for radiological intervention (such as embolization) and/or re-laparotomy to stop bleeding. Evidence of intra-abdominal bleeding should be obtained by imaging or blood loss via the abdominal drains if present. Transfusion of up to two units of PRBC is considered as being Grade A PHH. Grade B PHH requires transfusion of more than two units of PRBC, whereas the need for invasive re-intervention such as embolization and/ or re-laparotomy defines Grade C PHH. Conclusion: The proposed definition and grading of severity of PHH enables valid comparisons of results from different studies. It is easily applicable in clinical routine and should be applied in future trials to standardize reporting of complications. © 2011 International Hepato-Pancreato-Biliary Association.


Rahbari N.N.,University of Heidelberg | Garden O.J.,University of Edinburgh | Padbury R.,Flinders Medical Center | Brooke-Smith M.,Flinders Medical Center | And 21 more authors.
Surgery | Year: 2011

Background: Posthepatectomy liver failure is a feared complication after hepatic resection and a major cause of perioperative mortality. There is currently no standardized definition of posthepatectomy liver failure that allows valid comparison of results from different studies and institutions. The aim of the current article was to propose a definition and grading of severity of posthepatectomy liver failure. Methods: A literature search on posthepatectomy liver failure after hepatic resection was conducted. Based on the normal course of biochemical liver function tests after hepatic resection, a simple and easily applicable definition of posthepatectomy liver failure was developed by the International Study Group of Liver Surgery. Furthermore, a grading of severity is proposed based on the impact on patients' clinical management. Results: No uniform definition of posthepatectomy liver failure has been established in the literature addressing hepatic surgery. Considering the normal postoperative course of serum bilirubin concentration and International Normalized Ratio, we propose defining posthepatectomy liver failure as the impaired ability of the liver to maintain its synthetic, excretory, and detoxifying functions, which are characterized by an increased international normalized ratio and concomitant hyperbilirubinemia (according to the normal limits of the local laboratory) on or after postoperative day 5. The severity of posthepatectomy liver failure should be graded based on its impact on clinical management. Grade A posthepatectomy liver failure requires no change of the patient's clinical management. The clinical management of patients with grade B posthepatectomy liver failure deviates from the regular course but does not require invasive therapy. The need for invasive treatment defines grade C posthepatectomy liver failure. Conclusion: The current definition of posthepatectomy liver failure is simple and easily applicable in clinical routine. This definition can be used in future studies to allow objective and accurate comparisons of operative interventions in the field of hepatic surgery. © 2011 Mosby, Inc.


Koch M.,University of Heidelberg | Garden O.J.,University of Edinburgh | Padbury R.,Flinders Medical Center | Rahbari N.N.,University of Heidelberg | And 21 more authors.
Surgery | Year: 2011

Background: Despite the potentially severe impact of bile leakage on patients' perioperative and long-term outcome, a commonly used definition of this complication after hepatobiliary and pancreatic operations has not yet been established. The aim of the present article is to propose a uniform definition and severity grading of bile leakage after hepatobiliary and pancreatic operative therapy. Methods: An international study group of hepatobiliary and pancreatic surgeons was convened. A consensus definition of bile leakage after hepatobiliary and pancreatic operative therapy was developed based on the postoperative course of bilirubin concentrations in patients' serum and drain fluid. Results: After evaluation of the postoperative course of bilirubin levels in the drain fluid of patients who underwent hepatobiliary and pancreatic operations, bile leakage was defined as bilirubin concentration in the drain fluid at least 3 times the serum bilirubin concentration on or after postoperative day 3 or as the need for radiologic or operative intervention resulting from biliary collections or bile peritonitis. Using this criterion severity of bile leakage was classified according to its impact on patients' clinical management. Grade A bile leakage causes no change in patients' clinical management. A Grade B bile leakage requires active therapeutic intervention but is manageable without relaparotomy, whereas in Grade C, bile leakage relaparotomy is required. Conclusion: We propose a simple definition and severity grading of bile leakage after hepatobiliary and pancreatic operative therapy. The application of the present proposal will enable a standardized comparison of the results of different clinical trials and may facilitate an objective evaluation of diagnostic and therapeutic modalities in the field of hepatobiliary and pancreatic operative therapy. © 2011 Mosby, Inc.


Maggio A.,Institute of Cancer Research and Treatment | Panaia R.,Institute of Cancer Research and Treatment | Garibaldi E.,Institute of Cancer Research and Treatment | Bresciani S.,Institute of Cancer Research and Treatment | And 3 more authors.
Tumori | Year: 2012

Aims and background. The impact of age on prostate cancer outcome has been controversial. The aim of the study was to evaluate the role of age on overall survival and disease-free survival in patients affected by prostate cancer when treated with 3D conformal radiation therapy. Methods and study design. From 1999 to 2005, 1002 patients with T1-T3 prostate cancer were treated with 3D conformal radiation therapy, delivering a median dose of 75.6, 66.6 and 45 Gy to the prostate, seminal vesicles and pelvic nodes (if necessary), respectively. Patients were divided into four groups (<65, 65-70, 70-75, >75 years) according to age at diagnosis. The relationship between age and both overall survival and disease-free survival was calculated with Kaplan-Meier analysis and the comparison between curves was performed by the logrank test. ROC analysis allowed assessment of the best age cutoff. Results. Mean age was 71 ± 6 years (median, 72). Median and mean follow-up was 71.4 and 69 months, respectively. In multivariate analysis, there was no significant difference in the distribution of disease risk between age groups. Analysis demonstrated that older age is a strong positive predictor of survival (odds ratio for stratified patients older than 70 years was <1). In fact, at the 90 month follow-up, overall survival and disease-free survival varied with age, increasing from 85% to 95% and from 78% to 94%, respectively. ROC curve analysis yielded a cutoff age value discriminating overall survival and disease-free survival of 72 years. Conclusions. Age is a strong positive predictor of overall survival and disease-free survival, playing a protective role for stratified patients up to 72 years of age. © II Pensiero Scientifico Editore downloaded by EXCERPTA MEDICA.


Ascierto P.A.,Instituto Nazionale Tumori Fondazione G Pascale | Simeone E.,Instituto Nazionale Tumori Fondazione G Pascale | Sileni V.C.,Veneto Institute of Oncology IOV IRCCS | Vecchio M.D.,Italian National Cancer Institute | And 17 more authors.
Cancer Investigation | Year: 2014

Of 93 patients with pretreated, BRAFV600 mutation-positive advanced melanoma who received vemurafenib or dabrafenib before (n = 45) or after (n = 48) treatment with ipilimumab 3 mg/kg, median overall survival (mOS) from first treatment was 9.9 and 14.5 months, respectively. Among patients treated with a BRAF inhibitor first, mOS from the end of BRAF inhibition was 1.2 months for those who did not complete ipilimumab treatment as per protocol, compared with 12.7 months for those who did (p < .001). Prospective, randomized studies are required to determine the optimal sequencing of ipilimumab and BRAF inhibitors in patients with BRAF-mutated metastatic melanoma. Copyright © 2014 Informa Healthcare USA, Inc.


Sileni V.C.,Oncology Institute of Veneto IRCCS | Pigozzo J.,Oncology Institute of Veneto IRCCS | Ascierto P.A.,Instituto Nazionale Tumori Fondazione G Pascale | Grimaldi A.M.,Instituto Nazionale Tumori Fondazione G Pascale | And 18 more authors.
Journal of Experimental and Clinical Cancer Research | Year: 2014

Background: Elderly patients with metastatic melanoma have different disease characteristics and a poorer prognosis than younger patients. Data from clinical trials and expanded access programmes (EAPs) suggest ipilimumab confers a consistent survival benefit and has a similar safety profile across different age groups of patients with metastatic melanoma. Here we report the efficacy and safety of ipilimumab 3 mg/kg in elderly patients enrolled in an EAP in Italy. Methods. Patients aged > 70 years with pretreated melanoma received ipilimumab 3 mg/kg every 3 weeks for four doses through an EAP. Tumour response was evaluated at baseline and after completion of induction therapy using immune-related response criteria and patients were monitored throughout the treatment period for adverse events (AEs), including immune-related AEs. Results: The immune-related disease control rate among 188 evaluable patients was 38%, including four patients with an immune-related complete response, 24 with an immune-related partial response and 44 with immune-related stable disease. Median progression-free survival (PFS) was 4.0 months and the 1-and 2-year PFS rates were 21% and 12%, respectively. Median overall survival (OS) was 8.9 months; 1-and 2-year OS rates were 38% and 22%, respectively. The safety profile of ipilimumab was consistent with that observed in the general population of the Italian EAP and treatment-related AEs generally resolved within a median of 2 weeks with treatment as per protocol-specific guidelines. Conclusions: These results suggest ipilimumab is a feasible treatment option in elderly patients with metastatic melanoma. Ipilimumab treatment was generally well tolerated and resulted in clinical benefit and extended survival in elderly patients treated at centres in Italy. © 2014 Chiarion Sileni et al.; licensee BioMed Central Ltd.

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