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Pancreatic Neoplasms: HELP
Articles by Stefano Cereda
Based on 22 articles published since 2009
(Why 22 articles?)
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Between 2009 and 2019, S. Cereda wrote the following 22 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Editorial Role of taxanes in pancreatic cancer. 2012

Belli, Carmen / Cereda, Stefano / Reni, Michele. · ·World J Gastroenterol · Pubmed #22969215.

ABSTRACT: Pancreatic cancer is one of the most deadly cancers and is characterized by a poor prognosis. Single agent gemcitabine, despite its limited activity and modest impact on disease outcome, is considered as the standard therapy in pancreatic cancer. Most of the combination regimens used in the treatment of this disease, also including the targeted agents, did not improve the outcome of patients. Also, taxanes have been tested as single agent and in combination chemotherapy, both in first line and as salvage chemotherapy, as another possible option for treating pancreatic cancer. The inclusion of taxanes in combination with gemcitabine as upfront therapy obtained promising results. Accordingly, taxanes, and above all, new generation taxanes, appear to be suitable candidates for further testing to assess their role against pancreatic cancer in various clinical settings.

2 Review Neoadjuvant therapy in resectable pancreatic cancer: a critical review. 2013

Belli, Carmen / Cereda, Stefano / Anand, Santosh / Reni, Michele. ·Department of Medical Oncology, San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy. belli.carmen@hsr.it ·Cancer Treat Rev · Pubmed #23122322.

ABSTRACT: BACKGROUND: Pancreatic cancer is among the deadliest tumors. Due to intrinsic chemo- and radio-resistance, surgical resection remains the only chance for cure. However surgery alone is unable to considerably improve survival and complementary chemotherapy and radiotherapy in a multimodal approach have been tested. Adjuvant chemotherapy yielded a modest outcome improvement, whereas the use of adjuvant chemoradiation is highly controversial. In this scenario, the neoadjuvant approach has a strong theoretical rationale, but limited information on the efficacy of this strategy is available. MATERIALS AND METHODS: This review critically overviews the current knowledge, the rationale, the available data and information on neoadjuvant treatment in resectable pancreatic cancer. RESULTS: The very early systemic dissemination of pancreatic cancer endorses the rationale for an up-front use of systemic therapy. However, evidence collected so far depends on retrospective data, small case series that did not balance the different characteristics of patients suitable for surgery before or after neoadjuvant chemotherapy. CONCLUSION: Currently there is no straightforward evidence to support the routine clinical use of this strategy. Only a properly designed randomized trial testing combination chemotherapy regimens selected on the basis of their efficacy and activity against metastatic disease can address this issue.

3 Clinical Trial (Ir)relevance of Metformin Treatment in Patients with Metastatic Pancreatic Cancer: An Open-Label, Randomized Phase II Trial. 2016

Reni, Michele / Dugnani, Erica / Cereda, Stefano / Belli, Carmen / Balzano, Gianpaolo / Nicoletti, Roberto / Liberati, Daniela / Pasquale, Valentina / Scavini, Marina / Maggiora, Paola / Sordi, Valeria / Lampasona, Vito / Ceraulo, Domenica / Di Terlizzi, Gaetano / Doglioni, Claudio / Falconi, Massimo / Piemonti, Lorenzo. ·Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy. piemonti.lorenzo@hsr.it reni.michele@hsr.it. · Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Department of Radiology, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Department of Pathology, IRCCS San Raffaele Scientific Institute, Milan, Italy. Vita-Salute San Raffaele University, Milan, Italy. · Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. Vita-Salute San Raffaele University, Milan, Italy. · Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy. piemonti.lorenzo@hsr.it reni.michele@hsr.it. ·Clin Cancer Res · Pubmed #26459175.

ABSTRACT: PURPOSE: We aimed to assess the safety and efficacy of metformin for treating patients with metastatic pancreatic cancer and to identify endocrine and metabolic phenotypic features or tumor molecular markers associated with sensitivity to metformin antineoplastic action. EXPERIMENTAL DESIGN: We designed an open-label, randomized, phase II trial to assess the efficacy of adding metformin to a standard systemic therapy with cisplatin, epirubicin, capecitabine, and gemcitabine (PEXG) in patients with metastatic pancreatic cancer. Patients ages 18 years or older with metastatic pancreatic cancer were randomly assigned (1:1) to receive PEXG every 4 weeks in combination or not with 2 g oral metformin daily. The primary endpoint was 6-months progression-free survival (PFS-6) in the intention-to-treat population. RESULTS: Between August 2010 and January 2014, we randomly assigned 60 patients to receive PEXG with (n = 31) or without metformin (n = 29). At the preplanned interim analysis, the study was ended for futility. PFS-6 was 52% [95% confidence interval (CI), 33-69] in the control group and 42% (95% CI, 24-59) in the metformin group (P = 0.61). Furthermore, there was no difference in disease-free survival and overall survival between groups. Despite endocrine metabolic modifications induced by metformin, there was no correlation with the outcome. Single-nucleotide polymorphism rs11212617 predicted glycemic response, but not tumor response to metformin. Gene expression on tumor tissue did not predict tumor response to metformin. CONCLUSIONS: Addition of metformin at the dose commonly used in diabetes did not improve outcome in patients with metastatic pancreatic cancer treated with standard systemic therapy. See related commentary by Yang and Rustgi, p. 1031.

4 Clinical Trial Hypofractionated image-guided IMRT in advanced pancreatic cancer with simultaneous integrated boost to infiltrated vessels concomitant with capecitabine: a phase I study. 2013

Passoni, Paolo / Reni, Michele / Cattaneo, Giovanni M / Slim, Najla / Cereda, Stefano / Balzano, Gianpaolo / Castoldi, Renato / Longobardi, Barbara / Bettinardi, Valentino / Gianolli, Luigi / Gusmini, Simone / Staudacher, Carlo / Calandrino, Riccardo / Di Muzio, Nadia. ·Department of Radiation Oncology, San Raffaele Scientific Institute, Milan, Italy. Electronic address: passoni.paolo@hsr.it. ·Int J Radiat Oncol Biol Phys · Pubmed #24267968.

ABSTRACT: PURPOSE: To determine the maximum tolerated radiation dose (MTD) of an integrated boost to the tumor subvolume infiltrating vessels, delivered simultaneously with radical dose to the whole tumor and concomitant capecitabine in patients with pretreated advanced pancreatic adenocarcinoma. METHODS AND MATERIALS: Patients with stage III or IV pancreatic adenocarcinoma without progressive disease after induction chemotherapy were eligible. Patients underwent simulated contrast-enhanced four-dimensional computed tomography and fluorodeoxyglucose-labeled positron emission tomography. Gross tumor volume 1 (GTV1), the tumor, and GTV2, the tumor subvolume 1 cm around the infiltrated vessels, were contoured. GTVs were fused to generate Internal Target Volume (ITV)1 and ITV2. Biological tumor volume (BTV) was fused with ITV1 to create the BTV+Internal Target Volume (ITV) 1. A margin of 5/5/7 mm (7 mm in cranium-caudal) was added to BTV+ITV1 and to ITV2 to create Planning Target Volume (PTV) 1 and PTV2, respectively. Radiation therapy was delivered with tomotherapy. PTV1 received a fixed dose of 44.25 Gy in 15 fractions, and PTV2 received a dose escalation from 48 to 58 Gy as simultaneous integrated boost (SIB) in consecutive groups of at least 3 patients. Concomitant chemotherapy was capecitabine, 1250 mg/m(2) daily. Dose-limiting toxicity (DLT) was defined as any treatment-related G3 nonhematological or G4 hematological toxicity occurring during the treatment or within 90 days from its completion. RESULTS: From June 2005 to February 2010, 25 patients were enrolled. The dose escalation on the SIB was stopped at 58 Gy without reaching the MTD. One patient in the 2(nd) dose level (50 Gy) had a DLT: G3 acute gastric ulcer. Three patients had G3 late adverse effects associated with gastric and/or duodenal mucosal damage. All patients received the planned dose of radiation. CONCLUSIONS: A dose of 44.25 Gy in 15 fractions to the whole tumor with an SIB of 58 Gy to small tumor subvolumes concomitant with capecitabine is feasible in chemotherapy-pretreated patients with advanced pancreatic cancer.

5 Clinical Trial Maintenance sunitinib or observation in metastatic pancreatic adenocarcinoma: a phase II randomised trial. 2013

Reni, Michele / Cereda, Stefano / Milella, Michele / Novarino, Anna / Passardi, Alessandro / Mambrini, Andrea / Di Lucca, Giuseppe / Aprile, Giuseppe / Belli, Carmen / Danova, Marco / Bergamo, Francesca / Franceschi, Enrico / Fugazza, Clara / Ceraulo, Domenica / Villa, Eugenio. ·S. Raffaele Scientific Institute, Milan, Italy. Electronic address: reni.michele@hsr.it. ·Eur J Cancer · Pubmed #23899530.

ABSTRACT: 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 37.5mg 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); 2 y 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 2 y overall survival was remarkably high, suggesting that maintenance sunitinib is promising and should be further explored in this patient population.

6 Clinical Trial Feasibility and safety of EUS-guided cryothermal ablation in patients with locally advanced pancreatic cancer. 2012

Arcidiacono, Paolo Giorgio / Carrara, Silvia / Reni, Michele / Petrone, Maria Chiara / Cappio, Stefano / Balzano, Gianpaolo / Boemo, Cinzia / Cereda, Stefano / Nicoletti, Roberto / Enderle, Markus Dominik / Neugebauer, Alexander / von Renteln, Daniel / Eickhoff, Axel / Testoni, Pier Alberto. ·Division of Gastroenterology and Gastrointestinal Endoscopy, Vita-Salute San Raffaele University-Scientific Institute San Raffaele, Milan, Italy. arcidiacono.paologiorgio@hsr.it ·Gastrointest Endosc · Pubmed #23021160.

ABSTRACT: BACKGROUND: New therapies are needed for pancreatic cancer. OBJECTIVE: To determine the feasibility and safety of a new endoscopic treatment. Secondary endpoints were to determine effects on tumor growth measured with CT scan and to find the overall survival. DESIGN: A cohort study of patients with local progression of advanced pancreatic adenocarcinoma after neoadjuvant therapy. The cryotherm probe (CTP), a flexible bipolar device that combines radiofrequency with cryogenic cooling, was used under EUS guidance. SETTING: San Raffaele Hospital, Milan, Italy; University Medical Center, Hamburg-Eppendorf, Germany. PATIENTS: A total of 22 patients (male/female 11/11; mean age 61.9 years) were enrolled from September 2009 to May 2011. INTERVENTION: Radiofrequency heating: 18 W; pressure for cooling: 650 psi (Pounds per Square Inch); application time: depending on tumor size. MAIN OUTCOME MEASUREMENTS: Feasibility was evaluated during the procedure. A clinical and radiologic follow-up was planned. RESULTS: The CTP was successfully applied in 16 patients (72.8%); in 6 it was not possible because of stiffness of the GI wall and of the tumor. Amylase arose in 3 of 16 patients; none had clinical signs of pancreatitis. Late complications arose in 4 cases: 3 were mostly related to tumor progression. Median postablation survival time was 6 months. A CT scan was performed in all patients, but only in 6 of 16 was it possible to clearly define the tumor margins after ablation. In these patients, the tumor appeared smaller compared with the initial mass (P = .07). LIMITATIONS: Small sample of patients, difficulty of objectifying the size of the ablated zone by CT scan. CONCLUSION: EUS-guided CTP ablation is feasible and safe. Further investigations are needed to demonstrate progression-free survival and local control.

7 Clinical Trial Adjuvant PEFG (cisplatin, epirubicin, 5-fluorouracil, gemcitabine) or gemcitabine followed by chemoradiation in pancreatic cancer: a randomized phase II trial. 2012

Reni, Michele / Balzano, Gianpaolo / Aprile, Giuseppe / Cereda, Stefano / Passoni, Paolo / Zerbi, Alessandro / Tronconi, Maria Chiara / Milandri, Carlo / Saletti, Piercarlo / Rognone, Alessia / Fugazza, Clara / Magli, Alessandro / Di Muzio, Nadia / Di Carlo, Valerio / Villa, Eugenio. ·Department of Oncology, S. Raffaele Scientific Institute, Milan, Italy. reni.michele@hsr.it ·Ann Surg Oncol · Pubmed #22237835.

ABSTRACT: BACKGROUND: Information from randomized trials on the role of combination chemotherapy in the adjuvant treatment of pancreatic adenocarcinoma is limited. This randomized phase II trial aimed to identify the most promising regimen warranting phase III evaluation. METHODS: Therapy-naive patients, age 18-75 years, Karnofsky Performance Status (KPS)>60, gross total resection of stage IB-III pancreatic adenocarcinoma, stratified for center and surgical margins, were randomly assigned to receive either gemcitabine 1 g/m2 weekly on days 1, 8, and 15 (arm A) or the PEFG regimen (cisplatin and epirubicin 40 mg/m2, day 1; gemcitabine 600 mg/m2, days 1, 8; 5-fluorouracil 200 mg/m2 daily, days 1-28) (arm B). Chemotherapy was administered every 4 weeks for 3 months and followed by irradiation concurrent to continuous infusion of 5-fluorouracil 250 mg/m2 daily. Primary endpoint was the probability of being disease-free at 1 year from surgery. Assuming P0=35% and P1=55%, α=.05 and β=.10, the study was to enroll 51 patients per arm. RESULTS: A total of 102 patients were randomized; 100 were eligible (arm A: 51; arm B: 49). Baseline characteristic (A/B) were: Median age was 61/60 years; 75% had KPS>80 75/76%; 36% grade 3 tumor 29/43%, 79% stage IIB/III 75/84%, 31% R1 resection 35/29%. Survival figures (A/B) were: Median disease-free survival was 11.7 and 15.2 months; 1-year disease-free survival 49.0% (95% confidence interval [95% CI] 35-63%) and 69.4% (95% CI 56-83%); median survival 24.8 and 28.9 months. Combination chemotherapy produced more hematological toxicity without relevant differences in nonhematological toxicities. CONCLUSIONS: The 4-drug regimen deserves further assessment in resectable pancreatic cancer.

8 Clinical Trial A randomized phase II trial of two different 4-drug combinations in advanced pancreatic adenocarcinoma: cisplatin, capecitabine, gemcitabine plus either epirubicin or docetaxel (PEXG or PDXG regimen). 2012

Reni, Michele / Cereda, Stefano / Rognone, Alessia / Belli, Carmen / Ghidini, Michele / Longoni, Simonetta / Fugazza, Clara / Rezzonico, Sara / Passoni, Paolo / Slim, Najla / Balzano, Giampaolo / Nicoletti, Roberto / Cappio, Stefano / Doglioni, Claudio / Villa, Eugenio. ·Department of Oncology, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy. reni.michele@hsr.it ·Cancer Chemother Pharmacol · Pubmed #21626049.

ABSTRACT: PURPOSE: PEFG regimen (P:cisplatin, E:epirubicin, F:5-fluorouracil, G:gemcitabine) significantly prolonged progression-free (PFS) and overall survival (OS) of patients with advanced pancreatic adenocarcinoma (PA) with respect to standard gemcitabine. The current trial was aimed at assessing whether the replacement of E with docetaxel (D) may improve 6 months PFS (PFS6). METHODS: Chemo-naive patients with stage III or metastatic PA received P (30 mg/m(2) day 1 and 15), G (800 mg/m(2) day 1 and 15), and capecitabine (1,250 mg/m(2)/day days 1-28, without a break) and were randomized to receive either D at 25-30 mg/m(2) day 1 and 15 (arm A: PDXG regimen) or E at 30 mg/m(2) day 1 and 15 (arm B: PEXG regimen). Cycles were repeated every 28 days for a maximum of 6 months. The Fleming design was used to calculate the sample size on the probability of being PFS6. Assuming P0 = 40% and P1 = 60%, α = 0.05 and β = 0.10; the study was to enroll 52 patients per arm. RESULTS: Between July 2005 and September 2008, 105 patients were enrolled, stratified by stage and randomized. Patients' characteristics were (A/B) the following: median age 61/59, PS >70 92/88%, metastatic disease 66/65%. PFS6 was 58%, and median OS was 11 months in both arms. A partial response was observed in 60/37% of patients. Main per cycle G3-4 toxicity was the following: neutropenia 4/13%, thrombocytopenia 2/4%, anemia 4/4%, and fatigue 6/3%. CONCLUSIONS: The inclusion of D instead of E yielded more objective response and less G3-4 neutropenia but did not improve PFS and OS. The present trial confirms the relevant impact on outcome of advanced PA of 4-drug regimens.

9 Clinical Trial Salvage therapy with mitomycin and ifosfamide in patients with gemcitabine-resistant metastatic pancreatic cancer: a phase II trial. 2011

Cereda, Stefano / Reni, Michele / Rognone, Alessia / Fugazza, Clara / Ghidini, Michele / Ceraulo, Domenica / Brioschi, Matteo / Nicoletti, Roberto / Villa, Eugenio. ·Department of Oncology, S. Raffaele Scientific Institute, Milan, Italy. ·Chemotherapy · Pubmed #21454973.

ABSTRACT: BACKGROUND: At the time of upfront treatment failure, over half of the patients with advanced pancreatic cancer are candidates for further treatment. METHODS: Patients with metastatic gemcitabine-resistant pancreatic cancer were treated with mitomycin 8 mg/m(2) on day 1, ifosfamide 2,500 mg/m(2) and mesna 3,000 mg/m(2) on days 1-3 every 28 days until progressive disease. A positive responder was defined as a patient who was progression free at 6 months from trial enrollment. According to the Fleming design, a sample size of 34 patients was estimated assuming p0 = 0.05 and p1 = 0.20. RESULTS: Between May 2006 and December 2007, 21 patients (median age 56 years; median Karnofsky performance score 80) were enrolled. One patient died before receiving any treatment. Eighteen patients interrupted chemotherapy due to progressive disease (n = 15), toxicity (n = 2) or refusal (n = 1). Grade >2 toxicity consisted of neutropenia in 80% of patients, thrombocytopenia and fatigue in 20% and anemia in 10%. Only 1 patient was progression free at 6 months (5%). One patient had a partial response (5%) and 2 patients had stable disease (10%). Median survival was 3.7 months. CONCLUSION: Based on the poor outcome observed and on the high level of grade 3-4 toxicity, the trial was prematurely stopped and the mitomycin and ifosfamide regimen was considered insufficiently active in gemcitabine-pretreated advanced pancreatic cancer.

10 Clinical Trial Weekly epirubicin as salvage therapy in patients with gemcitabine-resistant advanced pancreatic cancer. 2009

Cereda, S / Rognone, A / Mazza, E / Fugazza, C / Ceraulo, D / Villa, E / Reni, M. ·Department of Oncology, S. Raffaele Scientific, Institute, Milan, Italy. ·J Chemother · Pubmed #20071296.

ABSTRACT: -- No abstract --

11 Clinical Trial Outcome of upfront combination chemotherapy followed by chemoradiation for locally advanced pancreatic adenocarcinoma. 2009

Reni, Michele / Cereda, S / Balzano, G / Passoni, P / Rognone, A / Zerbi, A / Nicoletti, R / Mazza, E / Arcidiacono, P G / Di Carlo, V / Villa, E. ·Department of Oncology, S. Raffaele Scientific Institute, via Olgettina 60, Milan 20132, Italy. reni.michele@hsr.it ·Cancer Chemother Pharmacol · Pubmed #19381632.

ABSTRACT: PURPOSE: The role and timing of chemotherapy and radiation for treating stage III pancreatic adenocarcinoma remains controversial. METHODS: Treatment-naive patients with stage III non-resectable pancreatic adenocarcinoma were treated with PEFG/PEXG (cisplatin, epirubicin, 5-fluorouracil (F)/capecitabine (X), gemcitabine) or PDXG (docetaxel substituting epirubicin) regimen for 6 months followed by radiotherapy (50-60 Gy) with concurrent F or X or G. RESULTS: Ninety-one patients were registered between April 1997 and December 2007. Forty-three patients (47%) had a partial remission and 38 (42%) had a stable disease. Thirteen patients (14%) were radically resected yielding one pathologic complete remission. Median survival (OS) was 16.2 months. Median progression-free survival was 9.9 months. Pattern of failure consisted of isolated local failure (N = 26, 35%); both local and systemic failure (N = 14, 19%); isolated systemic failure (N = 35, 47%). CONCLUSION: Combination chemotherapy with four-drug regimens followed by chemoradiation was a feasible strategy showing relevant results in stage III pancreatic adenocarcinoma.

12 Article Dosimetric and clinical predictors of toxicity following combined chemotherapy and moderately hypofractionated rotational radiotherapy of locally advanced pancreatic adenocarcinoma. 2013

Cattaneo, Giovanni M / Passoni, Paolo / Longobardi, Barbara / Slim, Najla / Reni, Michele / Cereda, Stefano / di Muzio, Nadia / Calandrino, Riccardo. ·Medical Physics Department, San Raffaele Scientific Institute, Milan, Italy. cattaneo.mauro@hsr.it ·Radiother Oncol · Pubmed #23726116.

ABSTRACT: BACKGROUND AND PURPOSE: Hypofractionated radiotherapy (RT) of pancreatic adenocarcinoma is limited by the tolerance of adjacent normal tissues. A better understanding of the influence of dosimetric variables on the rate of toxicity after RT must be considered an important goal. METHODS AND MATERIALS: Sixty-one patients with histologically proven locally advanced disease (LAPD) were analyzed. The therapeutic strategy consisted of induction chemotherapy (ChT) followed by concurrent chemoradiotherapy (CRT). In 39 out of 61 patients the target volume was based on a four-dimensional CT (4D-CT) procedure. Delivered dose was 44.25Gy in 15 fractions to PTV2, which consisted of pancreatic tumor and regional lymph nodes considered radiologically involved; 23 out of 61 patients received a simultaneous integrated boost (SIB) to a tumor sub-volume infiltrating the great abdominal vessels (PTV1) with dose in the range of 48-58Gy. RT was delivered with Helical Tomotherapy. Dose-volume histograms (DVHs) of target volumes and organs at risk (OARs) were collected for analysis. The predictive value of clinical/dosimetric parameters was tested by univariate/multivariate analyses. RESULTS: The crude incidence of acute gastrointestinal (GI) grade 2 toxicity was 33%. The 12-month actuarial rate of "anatomical" (gastro-duodenal mucosa damage) toxicity was 13% (95% CI: 4-22%). On univariate analysis, several stomach and duodenum DVH endpoints are predictive of toxicity after moderately hypofractionated radiotherapy. Multivariate analysis confirmed that baseline performance status and the stomach V20[%] were strong independent predictors of acute GI grade ⩾2 toxicity. The high-dose region of duodenum DVH (V45[%]; V40[%]) was strongly correlated with grade ⩾2 "anatomical" toxicity; the best V40[%] and V45[%] cut-off values were 16% and 2.6% respectively. CONCLUSION: Regarding dosimetric indices, stomach V20[%] correlates with a higher rate of acute toxicity; more severe acute and late anatomical toxicities are related to the high dose region of duodenum DVH.

13 Article Prognostic factors in gemcitabine-cisplatin polychemotherapy regimens in pancreatic cancer: XPD-Lys751Gln polymorphism strikes back. 2013

Avan, Amir / Pacetti, Paola / Reni, Michele / Milella, Michele / Vasile, Enrico / Mambrini, Andrea / Vaccaro, Vanja / Caponi, Sara / Cereda, Stefano / Peters, Godefridus J / Cantore, Maurizio / Giovannetti, Elisa. ·Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands. ·Int J Cancer · Pubmed #23390054.

ABSTRACT: The use of platinated agents in combination chemotherapy regimens for advanced pancreatic cancer is controversial owing to the lack of an outstanding impact on the outcome and a substantial increase in hematologic and extra-hematologic toxicities. Pharmacogenetic studies to identify patients who could benefit most from such therapies are urgently needed. The Xeroderma-Pigmentosum group-D polymorphism at codon-751 (XPD-Lys751Gln) emerged as the most significant independent predictor for death- and progression-risk in our previous study on functional polymorphisms in 122 advanced pancreatic cancer patients treated with cisplatin-docetaxel-capecitabine-gemcitabine and cisplatin-epirubicin-capecitabine-gemcitabine (or EC-GemCap). To confirm the prognostic role of this variable, we further evaluated the correlation of XPD-Lys751Gln with outcome in another 125 patients treated with the same regimens, and 90 treated with gemcitabine monotherapy. Genotyping was successfully carried out in the vast majority of DNA samples. Genotype frequencies followed Hardy-Weinberg equilibrium, and XPD-Lys751Gln was associated with differential progression-free and overall-survival. Multivariate analysis confirmed its prognostic significance in platinum-based regimens. In particular, XPD-Gln751Gln was significantly associated with risk of death (hazard ratio, HR = 1.7, 95% confidence interval [CI], 1.1-2.6, p = 0.011) and risk of progression (HR = 1.7, 95% CI, 1.1-2.5, p = 0.013). No correlation was observed in gemcitabine monotherapy-treated patients. The analysis of DNA damage using extra-long-PCR in lymphocytes supported the association of XPD-Gln751Gln with greater resistance to cisplatin-induced damage. The increasing evidence of XPD-Lys751Gln impact on the outcome of gemcitabine-cisplatin-based polychemotherapy leads to plan prospective studies to validate the role of this polymorphism as a new tool for optimization of the currently available treatments in pancreatic cancer.

14 Article Preoperative chemotherapy does not adversely affect pancreatic structure and short-term outcome after pancreatectomy. 2013

Pecorelli, Nicolò / Braga, Marco / Doglioni, Claudio / Balzano, Gianpaolo / Reni, Michele / Cereda, Stefano / Albarello, Luca / Castoldi, Renato / Capretti, Giovanni / Di Carlo, Valerio. ·Department of Surgery, Vita-Salute San Raffaele University, Via Olgettina 60, 20132, Milan, Italy. ·J Gastrointest Surg · Pubmed #23132627.

ABSTRACT: BACKGROUND: Preoperative chemotherapy (PCHT) has recently been proposed also in patients with resectable pancreatic adenocarcinoma. Few data are currently available on the impact of PCHT on short-term postoperative outcome after pancreatic resection. The objective of this study is to assess the impact of PCHT on pancreatic structure and short-term outcome after surgical resection. METHODS: Fifty consecutive patients successfully underwent resection after PCHT. Each patient was matched with two control patients with pancreatic adenocarcinoma selected from our prospective electronic database. Match criteria were age (±3 years), gender, American Society of Anesthesiologist score, type of resection, pancreatic duct diameter (±1 mm), and tumor size (±5 mm). Primary endpoint was morbidity rate. Secondary endpoints were pancreatic parenchymal structure, mortality rate, and length of hospital stay (LOS). RESULTS: Both degree of fibrosis and fatty infiltration of the pancreas were similar in the two groups. Overall morbidity rate was 48.0 % in the PCHT group vs. 54.0 % in the control group (p = 0.37). Pancreatic fistula rate was 18.0 % in the PCHT group vs. 25.0 % in the control group (p = 0.41). Mortality was 4.0 % in the PCHT group vs. 2.0 % in the control group (p = 0.60). Mean LOS (days) was 12.7 in the PCHT group vs. 12.4 in the control group (p = 0.74). There was no difference in resection margin status, while the rate of patients without nodal involvement was higher in the PCHT group (46.0 vs. 23.0 %, p = 0.004). CONCLUSION: PCHT did not induce significant structural changes in pancreatic parenchyma and did not adversely affect short-term outcome after surgery.

15 Article Biglycan expression and clinical outcome in patients with pancreatic adenocarcinoma. 2013

Aprile, Giuseppe / Avellini, Claudio / Reni, Michele / Mazzer, Micol / Foltran, Luisa / Rossi, Diego / Cereda, Stefano / Iaiza, Emiliana / Fasola, Gianpiero / Piga, Andrea. ·Department of Oncology, University Hospital "S Maria della Misericordia" of Udine, Piazzale S Maria della Misericordia, 33100, Udine, Italy. aprile.giuseppe@aoud.sanita.fvg.it ·Tumour Biol · Pubmed #23007878.

ABSTRACT: Conflicting results have been reported on the role of extracellular matrix (ECM) proteins in pancreatic cancer. Preclinical studies suggest that the overexpression of biglycan (proteoglycan-I, PG-I), a leucine-rich protein of the ECM, may induce growth arrest of pancreatic cancer cells. The aim of this study was to assess the prognostic role of biglycan expression in pancreatic cancer. We also evaluated MIB-1 and COX-2 expressions (as potential markers of growth and aggressiveness) to better characterize the biology of the tumors. The classical pathological parameters (grading, desmoplasia, perineural, or vascular invasion) as well as molecular determinants of prognosis were examined. MIB-1 (a proliferative index associated with prognosis in most tumors), COX-2, and PG-I expressions were detected by immunohistochemistry and immunofluorescence on tissue samples from 53 patients with pancreatic cancer and reviewed by two independent pathologists. To verify PG-I expression, three rabbit sera (LF104, LF112, and LF121 from NIH, Bethesda, MA, US) were tested. Logrank test and Cox's model were applied for statistical analysis. Out of 53 patients, 40 had stage III and IV pancreatic cancer. Fourteen patients did not express any of the PG-I epitopes. The patients who expressed at least two PG-I epitopes had shorter survival compared to those with single epitope or lacking any expression (28 vs 44 weeks, P = 0.0021). The MIB-1 higher expression predicted shorter survival (25 vs 41 weeks, P = 0.0059). The other parameters were not associated with clinical outcome. Multivariate analyses confirmed PG-I expression and MIB-1 as independent negative prognostic factors. Patients who presented PG-I expression in the ECM had the worse prognosis compared to those who did not. Our results are not in contrast with the hypothesis that ECM proteins are a potential barrier to metastatic spread in localized pancreatic cancer. Rather, we underline the complexity of tumor-stroma interactions in the advanced stage of cancer and the need of further study.

16 Article Association between DNA-repair polymorphisms and survival in pancreatic cancer patients treated with combination chemotherapy. 2011

Giovannetti, Elisa / Pacetti, Paola / Reni, Michele / Leon, Leticia G / Mambrini, Andrea / Vasile, Enrico / Ghidini, Michele / Funel, Niccola / Lucchesi, Matteo / Cereda, Stefano / Peters, Godefridus J / Cantore, Maurizio. ·Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands. elisa.giovannetti@gmail.com ·Pharmacogenomics · Pubmed #22026922.

ABSTRACT: AIM: This multicenter study evaluated the association of 11 candidate polymorphisms in eight genes with outcome of pancreatic cancer patients treated with the equivalent polychemotherapeutic regimens: cisplatin/epirubicin/capecitabine/gemcitabine, cisplatin/docetaxel/capecitabine/gemcitabine and gemcitabine/capecitabine plus epirubicin/cisplatin intra-arterial infusion. PATIENTS & METHODS: Towards this end, polymorphisms were assessed in DNA from 122 pancreatic cancer stage-III/IV patients, and their associations with toxicity/response and progression-free survival (PFS) and overall survival were evaluated using Pearson-χ(2) and log-rank test. RESULTS: Patients harboring XPD Gln751Gln, XPD Asp312Asn + Asn312Asn or XRCC1 Arg399Gln + Gln399Gln genotypes had a worse prognosis. XPD Gln751Gln (hazard ratio: 1.9; p = 0.003), as well as a combination of over two risk genotypes (hazard ratio: 2.7; p < 0.001), emerged as independent predictors for death risk at multivariate analysis. No correlations were observed with toxicity. Conversely, XPD Gln751Gln was associated with shorter PFS, while the lack of association with overall survival/PFS in gemcitabine monotherapy-treated patients suggested its role only for platinum-based regimens. CONCLUSION: Polymorphisms of DNA-repair genes appear to be candidate biomarkers of primary resistance to gemcitabine/cisplatin-based polychemotherapeutic regimens. The relatively small sample size, coupled with the retrospective and exploratory design of the present study, imply that these results should be considered as hypothesis generators, and should be further evaluated in larger and adequately designed retrospective/prospective studies.

17 Article Treatment trends in metastatic pancreatic cancer patients: Is it time to change? 2011

Reni, Michele / Pasetto, Lara Maria / Passardi, Alessandro / Milella, Michele / Mambrini, Andrea / Cereda, Stefano / Aprile, Giuseppe / Tronconi, Maria Chiara / Berardi, Rossana / Cordio, Stefano / Sartori, Nora / Rognone, Alessia / Pederzoli, Paolo / Falconi, Massimo. ·Department of Oncology, San Raffaele Scientific Institute, Via olgettina 60, Milan, Italy. reni.michele@hsr.it ·Dig Liver Dis · Pubmed #21044873.

ABSTRACT: BACKGROUND: Since gemcitabine became the standard treatment for metastatic pancreatic adenocarcinoma, combination chemotherapy obtained conflicting impact on survival (OS). AIMS: To evaluate Italian treatment trends in metastatic pancreatic cancer. METHODS: Data on treatment outcome of 943 chemo-naive patients with pathological diagnosis of stage IV pancreatic adenocarcinoma treated between 1997 and 2007 in Italian centres were analysed. RESULTS: Four treatment groups could be identified: (1) single agent gemcitabine (N=529); (2) gemcitabine-platinating agent doublets (N=105); (3) gemcitabine-free three-drug intraarterial combination (N=75); (4) four-drug gemcitabine-cisplatin-fluoropyrimidine based combinations (N=170). Median and actuarial 1 y OS of the whole population were 6.2 months and 20%, respectively. Gemcitabine (median OS 5.1 months) appeared significantly inferior to gemcitabine-free triplets (median OS 6.0 months; p=.04), gemcitabine-platinating agent doublets (median OS 7.4 months; p=.00001), or gemcitabine-based four drug combinations (median OS 9.1 months; p<.00001). CONCLUSION: These data mirror the Italian clinical practice in the therapeutic management of pancreatic cancer and suggest that four-drug combination chemotherapy may be included amongst the candidate regimens for phase III testing.

18 Article XELIRI or FOLFIRI as salvage therapy in advanced pancreatic cancer. 2010

Cereda, Stefano / Reni, Michele / Rognone, Alessia / Ghidini, Michele / Belli, Carmen / Longoni, Simona / Fugazza, Clara / Brioschi, Matteo / Nicoletti, Roberto / Balzano, Gianpaolo / Passoni, Paolo / Villa, Eugenio. ·Department of Oncology, S Raffaele Scientific Institute, Milan, Italy. ·Anticancer Res · Pubmed #21115942.

ABSTRACT: BACKGROUND: More than half of patients with pancreatic adenocarcinoma (PA) are candidates for further treatment when they experience upfront treatment failure. PATIENTS AND METHODS: Patients with gemcitabine-resistant PA, age <76 years and Karnofski performance status (KPS) >50 were treated with a XELIRI or FOLFIRI regimen until progressive disease or a maximum of six months. As this was an observational study, no statistical design was performed. RESULTS: Between July 2007 and December 2009, 34 patients (median age 60 years; median KPS 90) were treated with XELIRI (26) or FOLFIRI (8) regimen. Grade >2 toxicity consisted of neutropenia in 9% of patients, anemia and fatigue in 3% and hand-foot syndrome in 12%. Median progression-free survival was two months (range 1-4). Maximum response was stable disease in four patients (12%). Median survival was 4.2 (range 1-15) months. CONCLUSION: Fluoropyrimidine and irinotecan combination does not seem to have any role in the treatment of gemcitabine-resistant PA.

19 Article An Italian study on treatment trends and outcomes of patients with stage III pancreatic adenocarcinoma in the gemcitabine era: is it time to change? 2010

Reni, Michele / Sartori, Nora / Mambrini, Andrea / Berardi, Rossana / Passardi, Alessandro / Milella, Michele / Cereda, Stefano / Tronconi, Maria Chiara / Aprile, Giuseppe / Cordio, Stefano / Pasetto, Lara Maria / Rognone, Alessia / Pederzoli, Paolo / Falconi, Massimo. ·Department of Oncology, San Raffaele Scientific Institute, via Olgettina 60, Milan, Italy. reni.michele@hsr.it ·Anticancer Drugs · Pubmed #20110805.

ABSTRACT: A series of 650 patients treated between 1997 and 2007 at 10 Italian centers was analyzed to assess treatment trends and efficacy in stage III pancreatic adenocarcinoma. Data on patient characteristics, treatment and outcomes were collected. The inclusion criteria were pathological diagnosis of stage III pancreatic adenocarcinoma; age more than 18 years, Eastern Cooperative Oncology Group performance status less than 3, and no past therapy. Most patients (95%) received up-front chemotherapy, which mainly consisted of gemcitabine alone (N=323), gemcitabine-based four-drug combinations (N=107), gemcitabine-platinum compound doublets (N=87), or intra-arterial gemcitabine-free triplets (N=57). The use of gemcitabine-platinum compound doublets increased over time (1997-2001: 2%; 2002-2007: 21%) whereas an inverse trend was observed for gemcitabine (71-61%). No overall survival (OS) difference was observed between patients enrolled in clinical trials and those not enrolled. The median and 1-year OS were 9.5 months and 35.5% for patients treated with gemcitabine; 8.9 months and 36.8% for those treated with gemcitabine-free intra-arterial triplets; 13.3 months and 55.8% for those treated with gemcitabine-platinating agent doublets; and 16.2 months and 62.6% for those treated with gemcitabine-based four-drug combinations. Moreover, the median and 1-year OS were 12.7 months and 51.4% in patients who underwent planned consolidation chemoradiation, and 8.4 months and 30.4% in patients who did not. The use of a strategy consisting of a gemcitabine-platinating agent containing chemotherapy followed by consolidation chemoradiation has been increasing over time and may represent a suitable choice in the therapeutic management of stage III pancreatic adenocarcinoma.

20 Article Carbohydrate antigen 19-9 change during chemotherapy for advanced pancreatic adenocarcinoma. 2009

Reni, Michele / Cereda, Stefano / Balzano, Gianpaolo / Passoni, Paolo / Rognone, Alessia / Fugazza, Clara / Mazza, Elena / Zerbi, Alessandro / Di Carlo, Valerio / Villa, Eugenio. ·Department of Oncology, S. Raffaele Scientific Institute, Milan, Italy. reni.michele@hsr.it ·Cancer · Pubmed #19353729.

ABSTRACT: BACKGROUND: Radiologic assessment of tumor response in pancreatic cancer is complicated by desmoplastic reactions within or around the tumor. The objective of this study was to evaluate the correlation between a decline in carbohydrate antigen 19-9 (CA 19-9) and survival in patients with advanced pancreatic cancer who received upfront chemotherapy. METHODS: CA 19-9 serum basal values were measured in 247 patients with advanced pancreatic cancer who were enrolled in 5 consecutive trials between 1997 and 2007. Survival curves were compared among patients who had a predefined CA 19-9 nadir variation (<50%. Group 1; 50% to 89%, Group 2; or >89%, Group 3). To eliminate guarantee-time bias, survival analysis was repeated using the landmark method. RESULTS: In both univariate and multivariate analysis, the basal CA 19-9 value significantly predicted survival. The median survival was 15.5 months for 34 patients who had normal basal CA 19-9 values, 11.9 months for 108 patients who had basal values between 38 U/mL and 1,167 U/mL, and 8 months for 105 patients who had basal values >1,167 U/mL. At least 1 CA 19-9 follow-up value was available for 204 patients who had baseline values greater than normal. A significant difference in overall survival was observed in univariate and multivariate analyses between Groups 1 and 2, between Groups 1 and 3, and between Groups 2 and 3. The results were confirmed using the landmark method. CONCLUSIONS: In this study, baseline CA 19-9 was confirmed as an independent prognostic factor for survival, and it may be considered as a stratification factor in trials in patients with advanced pancreatic cancer. Biochemical response may be used as a complementary measure to radiologic response to provide a better assessment of chemotherapy activity and to drive treatment decisions in clinical practice.

21 Minor In reply to Ren et al. 2014

Passoni, Paolo / Reni, Michele / Cattaneo, Giovanni M / Slim, Najla / Cereda, Stefano. ·Department of Radiation Oncology, San Raffaele Scientific Institute, Milan, Italy. · Department of Medical Oncology, San Raffaele Scientific Institute, Milan, Italy. · Department of Medical Physics, San Raffaele Scientific Institute, Milan, Italy. ·Int J Radiat Oncol Biol Phys · Pubmed #24837892.

ABSTRACT: -- No abstract --

22 Minor Unity is strength: one, two, or more drugs against advanced pancreatic cancer? 2011

Reni, M / Cereda, S / Belli, C / Villa, E. · ·Ann Oncol · Pubmed #21289365.

ABSTRACT: -- No abstract --