Stefano Cascinu

Università Politecnica delle Marche, Ancona, The Marches, Italy

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Publications (351)1539.34 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Although the extended RAS analysis allows a better identification of patients potentially candidates to anti-EGFR monoclonal antibodies, a significant proportion of tumours may still reveals refractory to such a treatment approach. In these latter cases patients are then exposed to unnecessary toxicities without clinical benefit. Among many further biological factors that may have a role in determining resistance/sensitivity to EGFR-inhibitors, the EGFR itself, other members of the HER family (i.e. HER-2 and HER-3) as well as other surface receptors such as the IGF-1 receptor seem of particular interest. Preclinical models have shown that these receptors are biologically connected to each other and that they are able to directly or indirectly influence each other's downstream molecular pathways. In the presence of abnormal expression of these biological determinants, intracellular pathways may consequently become independent from receptor-targeting pharmacological modulations thus making treatment directed against the receptor ineffective. Clinical observations and translational studies seem to confirm these findings. The Authors have reviewed the literature and have selected recent clinical reports focusing on translational research on EGFR itself or on other molecules that may interfere with its pathway. With the aim to offer an effective tool for research and clinical practice, we also discuss on potential future developments.
    Current drug targets. 11/2014;
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    ABSTRACT: In November 1964, the recently founded American Society of Clinical Oncology (ASCO) held its first national meeting in Chicago (IL, USA). Only 51 members attended the conference. At the 2014 ASCO meeting, more than 30,000 healthcare professionals gathered together in the same city to attend this prime scientific conference. The many passionate attendees not only wanted to celebrate ASCO's 50th anniversary, but they also wanted to share the results of milestone clinical and translational research and, most notably, to consider future avenues of progress against cancer. In this report, the most significant advances in both clinical and translational research presented at the 2014 ASCO plenary session and oral abstract sessions will be discussed, specifically focusing on breast and colorectal carcinomas. Both of these are among the leading causes of cancer-related deaths. Many of the results presented significantly contribute to building a pipeline of novel treatment options. Moreover, these results will soon have an impact on clinical practice and may help medical oncologists move their research forward.
    Future Oncology 11/2014; 10(12):1901-1906. · 3.20 Impact Factor
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    ABSTRACT: Totally implantable central venous accesses (port-a-cath) are often used for chemotherapy administration or prolonged intravenous infusions in cancer patients. Local and systemic complications may occur both during and after placement of port-a-cath despite the well-established techniques for its placement and care. Out of other catheter-related local complications, thrombosis and infections represent the most common. Complications related to central venous catheter may be associated with infusion of both conventional chemotherapy and molecularly targeted therapy. Incidence and nature of complications of central venous catheter have been well established for long-term chemotherapy. However, very sparse data exists on the incidence of complications of molecularly targeted therapies administered through a central venous catheter. Hence, we decided to retrospectively analyze the local complications of a central venous catheter in patients receiving molecularly targeted therapy and conventional chemotherapy, respectively.
    Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 10/2014;
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    ABSTRACT: Aim: SIADH may be related to several causes (pulmonary disorders, CNS disturbances, drugs and chemotherapeutic agents), but in the majority of cases it is caused by malignancies. This observational study aimed to analyze treatments and outcome of SIADH in cancer pts. Methods: This study includes 69 consecutive cancer pts who experienced SIADH between 2010 and 2014 in 22 Italian Cancer Centers. Data on clinico-pathology, anticancer and SIADH treatments were recorded and statistically analized. Results: M/F ratio was 47/22, median age was 67 years (range 37-83). Primary tumor was lung cancer in 50 pts (SCLC in 39), while it was GI cancer in 8 pts. Fifty-eight pts were hospitalized due to SIADH, HN at admission was ≤130 mEq/l in 94.3%. Median duration of hospitalization was 13 days (range 3-90). 31 pts received tolvaptan for SIADH treatment (group A); other treatments included hypertonic saline solutions, diuretics, fluids restriction (group B). Group A included a significant higher N° of lung cancer pts (77.4% vs 68.4%) with metastatic disease (80.6% vs 76.3%). Moreover pts in group A had more severe HN at admission: serum sodium was ≤130 mEq/l in 96.7% pts and <120 mEq/l in 48% of pts, while in group B it was ≤130 mEq/l in 66.6% of pts and <120 mEq/l in 42.9%. Median sodium at the beginning of tolvaptan was 120 mEq/l (range 110-130), in group B it was 117 mEq/l (range 109-132). In group A 13 pts started tolvaptan 15 mg/daily, 4 started with 30 mg and 14 with 7.5 mg. No toxicity due to tolvaptan was observed in 25 pts, 6 experienced dry mouth. In 19 pts a dose change was required: in 4 it was increased to 30 mg/daily, while in the remaining 15 it was decreased to 7.5 mg every other day. HN improvement with tolvaptan was observed in all cases. Lenght of hospitalization was significantly longer in pts not receiving tolvaptan (15 days, range 4-100, vs 12 days, range 3-53 in pts receiving tolvaptan vs 8 days, range 1-41 in pts receiving tolvaptan since start of tolvaptan, p = 0.002). Severity of HN and not obtaining its correction correlated with lenght of stay and with overall survival (p < 0.05). Conclusions: To our knowledge this is the largest study analyzing SIADH in cancer pts to demonstrate that HN due to SIADH may result in a prolongation of hospitalization and in a worse overall survival when not adequately corrected and that tolvaptan represents an effective treatment potentially improving both. Disclosure: All authors have declared no conflicts of interest.
    09/2014; 25:517-541.
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    ABSTRACT: Increased neutrophil-to-lymphocyte ratio (NLR), an index of systemic inflammation, is associated with poor outcome for various types of cancers. We assessed the role on outcome prediction of NLR at baseline and persistent during first-line chemotherapy in patients with advanced urothelial cancer.
    Annals of Surgical Oncology 09/2014; · 4.12 Impact Factor
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    ABSTRACT: BACKGROUND: Bone is an uncommon site of metastasis in patients with advanced hepatocellular carcinoma (HCC). Therefore, there are few studies concerning the natural history of bone metastasis in patients with HCC. PATIENTS AND METHODS: Data on clinicopathology, survival, skeletal-related events (SREs), and bone-directed therapies for 211 deceased HCC patients with evidence of bone metastasis were statistically analyzed. RESULTS: The median age was 70 years; 172 patients were male (81.5%). The median overall survival was 19 months. The median time to the onset of bone metastasis was 13 months (22.2% at HCC diagnosis); 64.9% patients had multiple bone metastases. Spine was the most common site of bone metastasis (59.7%). Most of these lesions were osteolytic (82.4%); 88.5% of them were treated with zoledronic acid. At multivariate analysis, only the Child Score was significantly correlated with a shorter time to diagnosis of bone metastases (p = 0.001, HR = 1.819). The median survival from bone metastasis was 7 months. At multivariate analysis, HCC etiology (p = 0.005), ECOG performance status (p = 0.002) and treatment with bisphosphonate (p = 0.024) were associated with shorter survival after bone disease occurrence. The site of bone metastasis but not the number of bone lesions was associated with the survival from first skeletal related event (SRE) (p = 0.021) and OS (p = 0.001). CONCLUSIONS: This study provides a significant improvement in the understanding the natural history of skeletal disease in HCC patients. An early and appropriate management of these patients is dramatically needed in order to avoid subsequent worsening of their quality of life
    PLoS ONE 08/2014; · 3.53 Impact Factor
  • Expert Review of Anticancer Therapy 08/2014; · 3.22 Impact Factor
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    ABSTRACT: Hyponatraemia is one of the most common tumour-related electrolyte disorders. Several clinical, histological and serum factors have been found to influence prognosis, but, to date, there are no studies focusing on the prognostic role of hyponatraemia in mesothelioma. The aim of this study was to assess the prognostic role of hyponatraemia in malignant pleural mesothelioma.
    Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 08/2014;
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    ABSTRACT: Everolimus is a valid therapeutic option for neuroendocrine tumors (NETs); however, data in a real-world setting outside regulatory trials are sparse. The aim of this study was to determine everolimus tolerability and efficacy, in relation to previous treatments, in a compassionate use program. A total of 169 patients with advanced progressive NETs treated with everolimus were enrolled, including 85 with pancreatic NETs (pNETs) and 84 with nonpancreatic NETs (non-pNETs). Previous treatments included somatostatin analogs (92.9%), peptide receptor radionuclide therapy (PRRT; 50.3%), chemotherapy (49.7%), and PRRT and chemotherapy (22.8%). Overall, 85.2% of patients experienced adverse events (AEs), which were severe (grade 3-4) in 46.1%. The most frequent severe AEs were pneumonitis (8.3%), thrombocytopenia (7.7%), anemia (5.3%), and renal failure (3.5%). In patients previously treated with PRRT and chemotherapy, a 12-fold increased risk for severe toxicity was observed, with grade 3-4 AEs reported in 86.8% (vs. 34.3% in other patients). In addition, 63.3% of patients required temporarily everolimus discontinuation due to toxicity. Overall, 27.8% of patients died during a median follow-up of 12 months. Median progression-free survival (PFS) and overall survival (OS) were 12 months and 32 months, respectively. Similar disease control rates, PFS, and OS were reported in pNETs and non-pNETs. In the real-world setting, everolimus is safe and effective for the treatment of NETs of different origins. Higher severe toxicity occurred in patients previously treated with systemic chemotherapy and PRRT. This finding prompts caution when using this drug in pretreated patients and raises the issue of planning for everolimus before PRRT and chemotherapy in the therapeutic algorithm for advanced NETs.
    The Oncologist 08/2014; · 4.10 Impact Factor
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    ABSTRACT: Sunitinib malate (Sutent; Pfizer, Inc, New York, NY) is an oral multitargeted tyrosine kinase inhibitor that inhibits VEGF receptors (VEGFR-1, VEGFR-2, and VEGFR-3) among a family of kinase targets and have a central role in first-line treatment of metastatic renal cell carcinoma (mRCC). The approved schedule for sunitinib is 50 mg/day oid in the so called “4 weeks on and two weeks off” (4/2 schedule). Since treatment with sunitinib can be maintained for years, adequate treatment of adverse events (AEs) and care for quality of life is essential. For this reason, several alternative schedules have been proposed in order to personalize sunitinib administration and reduce related toxicity. This review discuss the efficacy and tolerability of alternative regimens to the standard 4/2 schedule that have been investigated in RCC patients including schedule of 50 mg/day 2-weeks on/1-week off, continuous schedule of 37.5 mg daily and the “Stop and Go strategy”.
    Critical Reviews in Oncology/Hematology 08/2014; · 4.64 Impact Factor
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    ABSTRACT: Historically, the cornerstone of treatment of advanced gastric cancer (GC) is 5-fluorouracil (5-FU)-based chemotherapy that increases median overall survival (OS) compared to best supportive care by some months. The addition of cisplatin (CDDP) to chemotherapy doublets showed a limited but significant benefit in term of OS according to a Cochrane meta-analysis. However, the recent individual patient-data GASTRIC meta-analysis, confirms this benefit in term of progression-free survival (PFS) but not OS, in randomized eight trials that include or not CDDP. The substitution of CDDP with a modern agent (oxaliplatin, irinotecan or taxanes) has been poorly evaluated in the literature. The REAL-2 phase III trial confirmed the equivalence of oxaliplatin and CDDP-based triplets, and a meta-analysis of three oxaliplatin-based randomized trials demonstrated that these combinations are better that CDDP-based doublets or triplets, improving both PFS (HR =0.88) and OS (HR =0.88). In particular, oxaliplatin-based chemotherapy was associated with less neutropenia and thromboembolic events, but with worse neurotoxicity. Given that the role of chemotherapy in advanced GC is palliative, CDDP-free regimens, and in particular oxaliplatin-based chemotherapy, may be considered for both CDDP-fit and unfit patients (that are those with poor renal function, older age, bad performance status or who cannot tolerate forced hydration for example). The limited absolute survival benefit of chemotherapy in advanced GC (few weeks at best), the cumbersome vascular toxicity of CDDP and the activity of several new drugs such irinotecan, oxaliplatin, taxanes and oral fluoropyrimidines make nowadays possible to consider CDDP-free regimens for the treatment of this incurable disease.
    Journal of gastrointestinal oncology 08/2014; 5(4):318-22.
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    ABSTRACT: Vascular endothelial growth factor (VEGF) is a potent inducer of tumor angiogenesis and represents the key element in the pathogenesis of clear cell renal cell carcinoma (ccRCC). The aim of this study was to investigate the use of tumor VEGF expression as a parameter to identify tumor stage and prognostically different patient groups.
    Urologic Oncology 07/2014; · 3.65 Impact Factor
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    ABSTRACT: Late recurrence of renal cell carcinoma (RCC) is not a rare event. The aim of this retrospective study was to investigate the clinico-pathological features and the outcome of patients (pts) treated with sorafenib, sunitinib and pazopanib for late-relapsing renal cell carcinoma (LR-RCC).
    The Journal of Urology 07/2014; · 3.75 Impact Factor
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    Matteo Santoni, Francesco Massari, Stefano Cascinu
    Cellular & molecular immunology 06/2014; · 3.42 Impact Factor
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    ABSTRACT: Introduction: Despite significant improvements in systemic chemotherapy over the last two decades, the prognosis of patients with advanced disease remains dismal. Collaborative, high-quality research and advances in high-throughput technologies have contributed to elucidate molecular pathways underpinning disease progression and have stimulated many clinical studies testing target therapies in the advanced disease setting. Although progress has been made thanks to trastuzumab in HER2 positive tumours, antiangiogenic drugs have produced conflicting results and EGFR-inhibitors have failed to show major improvements. Areas covered: While commenting on the results of many key Phase III randomized trials, the Authors discuss the most promising classes of novel targeted agents and present the current challenges toward a customized treatment. Expert opinion: Palliative chemotherapy became the worldwide standard of care for patients with advanced gastric cancers, producing significant life prolongation and improvement of life quality. Nevertheless, long-term outcomes of those patients remain poor. Because of the encouraging advancement in novel targeted therapies, such a disappointing scenario is now evolving. While results serve as a springboard for future research, more comprehensive efforts are needed to clarify the biological mechanisms underpinning cancer progression and help clinicians to develop new effective treatments.
    Expert Opinion on Investigational Drugs 05/2014; · 4.74 Impact Factor
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    ABSTRACT: Gastrointestinal Cancers Symposium 2014, San Francisco, CA, USA, 16-18 January 2014 The Gastrointestinal Cancers Symposium represents an indisputable occasion for sharing results and research opportunities for investigators around the globe. Across the years along with clinical trials presentations the meeting increasingly acquired a distinct role as a scientific arena for translational research. Also, this year the need for predictive markers for first-generation targeted agents and research about novel biologically driven therapeutic options characterized most of the studies presented. We focus here on reports from the 2014 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium indicating an opportunity for biological selection of either the pharmacological target or the patient population in order to enhance clinical outcome.
    Future oncology (London, England). 05/2014; 10(7):1125-8.
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    ABSTRACT: The anti-EGFR monoclonal antibodies panitumumab and cetuximab are effective in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer. We assessed the efficacy and toxicity of panitumumab versus cetuximab in these patients. For this randomised, open-label, phase 3 head-to-head study, we enrolled patients (from centres in North America, South America, Europe, Asia, Africa, and Australia) aged 18 years or older with chemotherapy-refractory metastatic colorectal cancer, an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less, and wild-type KRAS exon 2 status. Using a computer-generated randomisation sequence, we assigned patients (1:1; stratified by geographical region and ECOG performance status, with a permuted block method) to receive panitumumab (6 mg/kg once every 2 weeks) or cetuximab (initial dose 400 mg/m(2); 250 mg/m(2) once a week thereafter). The primary endpoint was overall survival assessed for non-inferiority (retention of ≥50% of the cetuximab treatment effect; historical hazard ratio [HR] for cetuximab plus best supportive care vs best supportive care alone of 0·55). The primary analysis included patients who received one or more dose of panitumumab or cetuximab, analysed per allocated treatment. Recruitment for this trial is closed. The trial is registered with ClinicalTrials.gov, number NCT01001377. Between Feb 2, 2010, and July 19, 2012, we enrolled and randomly allocated 1010 patients, 999 of whom began study treatment: 499 received panitumumab and 500 received cetuximab. For the primary analysis of overall survival, panitumumab was non-inferior to cetuximab (Z score -3·19; p=0·0007). Median overall survival was 10·4 months (95% CI 9·4-11·6) with panitumumab and 10·0 months (9·3-11·0) with cetuximab (HR 0·97; 95% CI 0·84-1·11). Panitumumab retained 105·7% (81·9-129·5) of the effect of cetuximab on overall survival seen in this study. The incidence of adverse events of any grade and grade 3-4 was similar across treatment groups. Grade 3-4 skin toxicity occurred in 62 (13%) patients given panitumumab and 48 (10%) patients given cetuximab. The occurrence of grade 3-4 infusion reactions was lower with panitumumab than with cetuximab (one [<0·5%] patient vs nine [2%] patients), and the occurrence of grade 3-4 hypomagnesaemia was higher in the panitumumab group (35 [7%] vs 13 [3%]). We recorded one treatment-related fatal adverse event: a lung infection in a patient given cetuximab. Our findings show that panitumumab is non-inferior to cetuximab and that these agents provide similar overall survival benefit in this population of patients. Both agents had toxicity profiles that were to be expected. In view of the consistency in efficacy and toxicity seen, small but meaningful differences in the rate of grade 3-4 infusion reactions and differences in dose scheduling can guide physician choice of anti-EGFR treatment. Amgen Inc.
    The Lancet Oncology 04/2014; · 25.12 Impact Factor
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    ABSTRACT: The objective of this study was to determine the impact of different metastatic spread patterns on outcome in advanced digestive neuroendocrine tumors (NETs). This was a retrospective analysis of patients with stage IV NETs, classified as group 1 (unilobar liver metastases), group 2 (bilobar liver metastases), group 3 (extra-abdominal metastases). End points were overall survival (OS) and progression-free survival (PFS). Risk factor analysis was performed using Cox proportional hazard model. Of the 229 patients, 135 (58.9%) had pancreatic, and 94 (41.1%) small bowel NETs: 32 (13.9%) were included in group 1, 179 (78.2%) in group 2, and 18 (7.9%) in group 3. Median Ki67 was 4.5%. Overall, 5-year OS was 55%. Different OS was observed among the 3 groups: median survival not reached, 81 and 8 months, respectively (P < 0.001). Median PFS was 18 months. Both OS and PFS were significantly affected by Ki67 and metastatic spread pattern. The stratification of stage IV NET patients based on metastatic patterns, alongside Ki67, predicts the clinical outcome. The extent of metastatic disease is a previously unrecognized variable, which should be considered when evaluating the results of treatments in NET patients with advanced disease.
    Pancreas 03/2014; 43(2):212-8. · 2.95 Impact Factor
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    ABSTRACT: Although new treatment modalities changed the global approach to hepatocellular carcinoma (HCC), this disease still represents a medical challenge. Currently the therapeutic stronghold is sorafenib, a tyrosine kinase inhibitor (TKI) directed against the vascular endothelial growth factor (VEGF) family. Previous observations suggested that polymorphisms of VEGF and its receptor (VEGFR) genes may regulate angiogenesis and lymphangiogenesis and thus tumour growth control. The aim of our study was to evaluate the role of VEGF and VEGFR polymorphisms in determining the clinical outcome of HCC patients receiving sorafenib. From a multicenter experience 148 samples (tumour or blood samples) of HCC patients receiving sorafenib were tested for VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs). Patients progression free survival (PFS) and overall survival (OS) were analysed. At univariate analysis VEGF-A alleles C of rs25648, T of rs833061, C of rs699947, C of rs2010963, VEGF-C alleles T of rs4604006, G of rs664393, VEGFR-2 alleles C of rs2071559, C of rs2305948 were significant predictors of PFS and OS. At multivariate analysis rs2010963, rs4604006 and BCLC (Barcelona Clinic Liver Cancer) stage, resulted to be independent factors influencing PFS and OS. Once prospectively validated, the analysis of VEGF and VEGFR SNPs may represent a clinical tool to better identify HCC patients more likely to benefit from sorafenib. On the other hand the availability of more accurate predictive factors could help avoiding unnecessary toxicities to potentially resistant patients who may be optimal candidates for different treatments interfering with other tumour molecular pathways. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 02/2014; · 6.20 Impact Factor
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    ABSTRACT: The mammalian target of rapamycin (mTOR) has emerged as an attractive cancer therapeutic target. Treatment of metastatic renal cell carcinoma (mRCC) has improved significantly with the advent of agents targeting the mTOR pathway, such as temsirolimus and everolimus. Unfortunately, a number of potential mechanisms that may lead to resistance to mTOR inhibitors have been proposed. In this paper, we discuss the mechanisms underlying resistance to mTOR inhibitors, which includes the downstream effectors of the phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway, the activation of hypoxia-inducible factor (HIF), the PIM kinase family, PTEN expression, elevated superoxide levels, stimulation of autophagy, immune cell response and ERK/MAPK, Notch and Aurora signaling pathways. Moreover, we present an updated analysis of clinical trials available on PubMed Central and www.clinicaltrials.gov, which were pertinent to the resistance to rapalogs. The new frontier of inhibiting the mTOR pathway is to identify agents targeting the feedback loops and cross talks with other pathways involved in the acquired resistance to mTOR inhibitors. The true goal will be to identify biomarkers predictive of sensitivity or resistance to efficiently develop novel agents with the aim to avoid toxicities and to better choose the active drug for the right patient.
    Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 01/2014; · 9.03 Impact Factor

Publication Stats

5k Citations
1,539.34 Total Impact Points

Institutions

  • 1970–2014
    • Università Politecnica delle Marche
      • Chair of Medical Oncology
      Ancona, The Marches, Italy
  • 2013
    • Azienda Ospedaliero Universitaria Ancona
      Ancona, The Marches, Italy
  • 2001–2013
    • University Hospital of Parma
      • Reparto di Oncologia medica
      Parma, Emilia-Romagna, Italy
  • 1989–2013
    • Ospedali Riuniti di Bergamo
      Bérgamo, Lombardy, Italy
  • 2007–2012
    • Azienda Ospedaliero - Universitaria "Ospedali Riuniti" Trieste
      Trst, Friuli Venezia Giulia, Italy
  • 2006–2012
    • LIUCBM Libera Università Campus Bio-Medico di Roma
      • Unit of Medical Oncology
      Roma, Latium, Italy
  • 2004–2006
    • Azienda Ospedaliera Ospedali Riuniti Papardo Piemonte
      Messina, Sicily, Italy
  • 1999–2006
    • Università degli Studi di Messina
      • • Dipartimento di Scienze Biomediche e delle Immagini Morfologiche e Funzionali
      • • Dipartimento di Medicina Clinica e Sperimentale
      Messina, Sicily, Italy
    • Azienda Ospedaliera Bianchi-Melacrino-Morelli di Reggio Calabria
      Reggio di Calabria, Calabria, Italy
  • 2005
    • Kanazawa Medical University
      • Department of Surgery II
      Kanazawa-shi, Ishikawa-ken, Japan
  • 2003
    • University-Hospital of Padova
      Padua, Veneto, Italy
  • 1997–2003
    • Università degli Studi di Siena
      Siena, Tuscany, Italy
  • 1993–1997
    • Azienda Ospedaliera San Carlo Borromeo Milano
      • Division of Medical Oncology
      Milano, Lombardy, Italy