S Ferrari

Istituto Ortopedico Rizzoli, Bolonia, Emilia-Romagna, Italy

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Publications (135)500.44 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The management of biliary tract cancers (BTCs) is complex due to limited data on the optimal therapeutic approach. This phase II multicenter study evaluated the efficacy and tolerability of vandetanib monotherapy compared to vandetanib plus gemcitabine or gemcitabine plus placebo in patients with advanced BTC. Patients were randomized in a 1:1:1 ratio to 3 treatment groups: vandetanib 300mg monotherapy (V), vandetanib 100mg plus gemcitabine (V/G), gemcitabine plus placebo (G/P). Vandetanib (300mg or 100mg) or placebo were given in single oral daily doses. Gemcitabine 1000mg/m(2) was intravenously infused on day 1 and day 8 of each 21-day cycle. The primary endpoint was progression-free survival (PFS). Secondary endpoints were: objective response rate (ORR), disease control rate, overall survival, duration of response, performance status and safety outcomes. 173 patients (mean age 63.6 years) were recruited at 19 centers across Italy. Median (95% confidence intervals) PFS (days) were 105 (72-155), 114 (91-193) and 148 (71-225) respectively for the V, V/G and G/P-treatment groups, with no statistical difference among them (P=0.18). No statistical difference between treatments was observed for secondary endpoints, except ORR, which slightly favored the V/G combination over other treatments. The proportion of patients reporting adverse events (AEs) was similar for the 3 groups (96.6% in V arm, 91.4% in the V/G arm and 89.3% in the G/P arm). Vandetanib treatment did not improve PFS in patients with advanced BTC. The safety profile of vandetanib did not show any additional AEs or worsening of already known AEs. NCT00753675. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
    Annals of Oncology 12/2014; 26(3). DOI:10.1093/annonc/mdu576 · 6.58 Impact Factor
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    ABSTRACT: Background: At diagnosis, identification of reliable biological indicators of prognosis to allow stratification of patients according to different risks is an important but still unresolved aspect in the treatment of Ewing sarcoma (EWS) patients. This study aimed to explore the role of miR-34A expression on prognosis of EWS patients. Patients and methods: Specimens from 109 patients with non-metastatic EWS treated at the Rizzoli Institute with neoadjuvant chemotherapy (protocols ISG/SSGIII, EW-1, EW-2, EW-REN2, EW-REN3, EW-PILOT) and 17 metastases were studied. Sixty-eight patients (62%) remained disease-free and 41 (38%) relapsed (median follow-up: 67 months, range 9-241 months). Expression of miR-34a and of some of its targets (cyclin D1, bcl-2, SIRT1 and YY1) was evaluated by qRT-PCR using TaqMan MicroRNA Assays and/or by immunohistochemistry on tissue microarrays from the same patients. Results: High expression of miR-34a in localized tumors was significantly related to better event-free and overall survival (P = 0.004). Relevance of miR-34a was confirmed by using different calibrators (normal mesenchymal stem cells and different normal tissues). By multivariate Cox regression analysis, low miR-34a expression as well as nontotal necrosis and high levels of lactate dehydrogenase were all confirmed as independent risk factors associated with poor outcome. Expression of miR-34a was lower in metastases than in primary tumors. It inversely correlated with expression of cyclin D1 and Ki-67. Conclusions: By demonstrating its relationship with clinical outcome, we propose evaluation of miR-34a at diagnosis of EWS patients to allow early risk stratification. Validation of these results would nonetheless ultimately need a prospective assessment.
    Annals of Oncology 07/2014; 25(10). DOI:10.1093/annonc/mdu249 · 6.58 Impact Factor
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    ABSTRACT: Teenagers and young adults (TYA) cancer contributes substantially to morbidity and mortality in a population with much to offer society. TYA place distinct challenges upon cancer care services, many reporting feeling marginalized and their needs not being met in adult or paediatric cancer services. Bone tumours such as osteosarcoma and Ewing sarcoma, because of their age at presentation and the complexity of their care, are where challenges in managing (TYA) with cancer have often been most readily apparent. Bone sarcomas may be managed by paediatric or medical oncologists, and require fastidious attention to protocol. A lack of recent improvement in survival in TYA with bone tumours may be linked to a lack of specialist care, poor concordance with therapy in some situations and TYA-specific pharmacology. Participation in clinical trials, particularly of young adults, is low, hindering progress. All these requirements may be best met by a concerted effort to create collaborative care between adult and paediatric experts in bone sarcoma, working together to meet TYA patients' needs.
    Annals of Oncology 06/2014; 25(8). DOI:10.1093/annonc/mdu153 · 6.58 Impact Factor
  • American Journal of Clinical Oncology 03/2013; · 2.61 Impact Factor
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    ABSTRACT: Background To explore correlation between the quality of surgery and outcome in high-risk soft tissue sarcoma (STS) patients treated within a phase III randomized trial.Patients and Methods In the trial, all patients received three cycles of preoperative chemotherapy (CT) with epirubicin 120 mg/m(2) and ifosfamide 9 g/m(2) and were randomly assigned to receive two further postoperative cycles. Radiotherapy (RT) could be delivered in the preoperative or postoperative setting. The association between surgical margins and overall survival (OS) was studied in a univariate and multivariate fashion.ResultsTwo hundred and fifty-two patients completed the whole treatment and were operated conservatively. At a median follow-up of 60 months (IQR, 45-74 months), the 5-year OS was 0.73, even in patients with positive and negative margins. The 5-year cumulative incidence (CI) of local recurrence (LR) in patients with positive and negative microscopic margins was 0.17 (standard error, SE, 0.08) and 0.03 (SE, 0.01), respectively. In the subgroup of patients receiving combined preoperative CT-RT and with positive surgical margins, the CI of LR was 0.Conclusions In this setting of high-risk STS treated by preoperative CT or CT-RT, the negative impact of positive margins on the outcome was limited. When close margins can be anticipated preoperative CT-RT may be a reasonable option to maximize the chance of cure.
    Annals of Oncology 10/2012; 24(3). DOI:10.1093/annonc/mds501 · 6.58 Impact Factor
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    ABSTRACT: Background The Italian Sarcoma Group and the Scandinavian Sarcoma Group designed a joint study to improve the prognosis for patients with Ewing's family tumors and synchronous metastatic disease limited to the lungs, or the pleura, or a single bone. Patients and methods The study was opened in 1999 and closed to the enrollment in 2008. The program consisted of intensive five-drug combination chemotherapy, surgery and/or radiotherapy as local treatment, and consolidation treatment with high-dose busulfan/melphalan plus autologous stem cell rescue and total-lung irradiation. Results During the study period, 102 consecutive patients were enrolled. The median follow-up was 62 months (range 24-124). The 5-year event-free survival probability was 0.43 [standard deviation (SD) = 0.05] and the 5-year overall survival probability was 0.52 (SD = 0.052). Unfavorable prognostic factors emerging on multivariate analysis were a poor histological/radiological response at the site of the primary tumor [relative risk (RR) = 3.4], and incomplete radiological remission of lung metastases after primary chemotherapy (RR = 2.6). One toxic death and one secondary leukemia were recorded. Conclusions This intensive approach is feasible and long-term survival is achievable in ∼50% of patients. New treatment approaches are warranted for patients responding poorly to primary chemotherapy.
    Annals of Oncology 07/2012; 23(11):2970-6. DOI:10.1093/annonc/mds117 · 6.58 Impact Factor
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    ABSTRACT: Bone metastatic patients with osteosarcoma have a very poor prognosis. Targeted radiation therapy has been pursued as a valid alternative. The primary end point of this study was progression-free survival (PFS) at 4 months. Twenty-two osteosarcoma patients were treated with Samarium-153 ethylenediaminetetramethylene phosphonic acid (153Sm-EDTMP) at various dosages. Administered activities ranged from 150 (3 mCi/kg) to 1140 MBq/kg (30 mCi/kg). Autologous hematopoietic stem cell infusion was carried out on day 14 after the (153)Sm-EDTMP infusion. The median PFS was 61 days (18-436 days) and the median overall survival (OS) was 189 days (31-1175 days). PFS and OS for the entire patient population were 32% [95% confidence interval (CI) 16-50] and 76% (95% CI 52-89) at 4 months, respectively. No statistical differences emerged according to 153Sm-EDTMP administered or 24-h retained activity. One-month pain palliation was only observed in a minority of subjects and in none at 4 months. Based on our series, the PFS is dramatically short even when higher activity of (153)Sm-EDTMP is administered. This would mean that, even at high level, 153Sm-EDTMP is itself ineffective against relapsed osteosarcoma or the residual activity is too low to be active on these particular subsets of patients.
    Annals of Oncology 11/2011; 23(7):1899-905. DOI:10.1093/annonc/mdr542 · 6.58 Impact Factor
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    ABSTRACT: Giant cell tumor (GCT) of bone is an aggressive neoplasm arising from the medullary and consisting of multinucleated osteoclast-like giant cells and proliferating osteoblast-like stromal cells. It is a rare neoplasm that accounts for approximately 5% of all primary bone tumors in adults, with an incidence of 1 case per million, and is slightly more prevalent in women than in men; it occurs most frequently at the end of long bones, but every bone can be affected. Curettage is the gold standard treatment, but unfortunately sometimes it is impossible because of lack of structural integrity of the segment, or the presence of a fracture or of a local relapse that is difficult to treat surgically. The use of local adjuvant treatment, as phenol or liquid nitrogen, is suggested to decrease the risk of recurrence. In selected cases resection and reconstruction with a prosthesis are recommended to decrease the risk of recurrence. Radiofrequency thermoablation and cryosurgery with probes should be used in the miniinvasive treatment of small lesions or in case of a local and difficult to treat recurrence. Anyway, a medical approach is the great news in the treatment of GCT. Denosumab is a fully human monoclonal antibody that inhibits RANKL, a protein essential for osteoclast formation, function, and survival. Good clinical, radiological and histological results have been reported in the treatment of GTC of bone with denosumab, but more studies are needed to assess its efficacy and side effects.
    LO SCALPELLO-OTODI Educational 10/2011; 25(3). DOI:10.1007/s11639-011-0125-3
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    ABSTRACT: To evaluate neoadjuvant trabectedin (1.5 mg/m(2) 24-h i.v. infusion every 3 weeks; three to six cycles) in patients with locally advanced myoxid liposarcoma (ML) previously untreated with chemotherapy or radiation. Primary efficacy end point was pathological complete response (pCR) or tumoral regression rate. Objective response according to RECIST (v.1.0) was a secondary end point. Three of 23 assessable patients had pCR [13%; 95% confidence interval (CI), 3% to 34%]. Furthermore, very good and moderate histological responses were observed in another 2 and 10 patients, respectively. Histological decrement in the cellular and vascular tumor component and maturation of tumor cells to lipoblasts were observed in both myoxid and myoxid/round cell variants. Seven patients had partial response according to RECIST (objective response rate of 24%; 95% CI, 10% to 44%). No disease progression was reported. Neoadjuvant trabectedin was usually well tolerated, with a safety profile similar to that described in patients with soft tissue sarcoma or other tumor types. Trabectedin 1.5 mg/m(2) given as a 24-h i.v. infusion every 3 weeks is a therapeutic option in the neoadjuvant setting of ML.
    Annals of Oncology 06/2011; 23(3):771-6. DOI:10.1093/annonc/mdr265 · 6.58 Impact Factor
  • Radiotherapy and Oncology 05/2011; 99. DOI:10.1016/S0167-8140(11)70797-6 · 4.86 Impact Factor
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    ABSTRACT: Purpose: After standard multimodal therapy, the prognosis of relapsed and unresectable high-grade osteosarcoma is dismal and unchanged over the last decades. Recently, mitogen-activated protein kinases were shown to be activated in osteosarcoma specimens, suggesting, therefore, they are suitable targets for the multikinase inhibitor sorafenib. Thus, we explored sorafenib activity in patients with relapsed and unresectable osteosarcoma. Experimental design: Patients > 14 years, progressing after standard treatment, were eligible to receive 400 mg of sorafenib twice daily until progression or unacceptable toxicity. The primary end point was progression-free survival (PFS) at 4 months. Secondary objectives were PFS, overall survival (OS), clinical benefit rate (CBR), defined as no progression at 6 months and safety. This nonrandomized phase II study used a Simon two-stage design. PFS and OS at 95% confidence intervals (95% CIs) were calculated by the Kaplan-Meier method. All tests were two sided. RESULTS: Thirty-five patients were enrolled. PFS at 4 months was 46% (95% CI 28% to 63%). Median PFS and OS were 4 (95% CI 2-5) and 7 (95% CI 7-8) months, respectively. The CBR was 29% (95% CI 13% to 44%). We observed 3 (8%) partial responses (PRs), 2 (6%) minor responses (< 30% tumor shrinkage) and 12 (34%) stable diseases (SDs). For six patients (17%), PR/SD lasted ≥ 6 months. Noteworthy, tumor density reduction and [(18)F]2-fluoro-2-deoxy-d-glucose-positron emission tomography responses were observed among SD patients. Sorafenib was reduced or briefly interrupted in 16 (46%) patients and permanently discontinued in one (3%) case due to toxicity. CONCLUSIONS: Sorafenib demonstrated activity as a second- or third-line treatment in terms of PFS at 4 months with some unprecedented long-lasting responses. Sorafenib, the first targeted therapy showing activity in osteosarcoma patients, deserves further investigations.
    Annals of Oncology 04/2011; 23(2):508-16. DOI:10.1093/annonc/mdr151 · 6.58 Impact Factor
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    ABSTRACT: Malignant peripheral nerve sheath tumours (MPNST) are rare sarcomas with one of the poorest prognoses of all the soft tissue sarcomas. Information about adjuvant treatment is scarce and not homogeneous for this diagnosis. We analyzed retrospectively the outcome of patients with localized high grade MPNST admitted to our institute from 1969 to 2008. A review of the literature is also reported. Of 62 evaluable patients, 23 were females and 39 males, median age 39 years (17-71), 22/62 had neurofibromatosis type I. Median follow-up was 54 months (range 12-194). A total of 22/62 are alive; 26 patients had surgery alone, 18 received radiation therapy, 12 received radiation therapy and chemotherapy, and 6 received only adjuvant chemotherapy. The 5-year disease-free survival was 30% and 5-year overall survival was 38%. A positive trend for adjuvant radiation, but not for chemotherapy was observed according to univariate analysis only for disease-free survival and overall survival. Multivariate analysis indicated that primary site, size and surgical margins remained significant for disease-free survival and only site and size were significant for overall survival. New drugs employed successfully in advanced mpNSt should be employed also in the adjuvant setting.
    Journal of chemotherapy (Florence, Italy) 01/2011; 22(6):413-8. DOI:10.1179/joc.2010.22.6.413 · 1.07 Impact Factor
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    ABSTRACT: High-dose chemotherapy (HDT) was added to conventional chemotherapy in Ewing sarcoma family tumor (EFT) patients, poor responders (PRs) to induction chemotherapy in order to improve their survival. Patients aged ≤40 years with nonmetastatic Ewing sarcoma (ES) received vincristine (V), doxorubicin (A), cyclofosfamide (C), actinomycin (Ac), ifosfamide (I) and etoposide (E) (VACAc-IE regimen) as induction chemotherapy. As maintenance treatment, good responders (GR) received nine cycles of VACAc-IE regimen. PRs received three cycles of VAC-IE, mobilizing cycle with CE and HDT with Busulfan and Melphalan with stem cell support. Three hundred patients [median age 15 years (3-40 years)] entered the study. One patient refused local treatment, 242 (81%) underwent surgery [with radiotherapy (RT) in 80] and 57 (19%) RT alone. No toxic deaths were recorded. Overall GR were 146 (49%). Twenty-eight PR did not receive HDT. At a median follow-up of 64 months (21-116 months), 5-year overall and event-free survival (EFS) were 75% and 69%, respectively. Five-year EFS was 75% for GR, 72% for PR treated with HDT and 33% for PR who did not receive HDT. High-dose therapy added to the VACA-IE regimen in PR patients is feasible and effective. Selected groups of patients with ES can benefit from HDT.
    Annals of Oncology 11/2010; 22(5):1221-7. DOI:10.1093/annonc/mdq573 · 6.58 Impact Factor
  • Annals of Oncology 05/2010; 21 Suppl 5:v204-13. DOI:10.1093/annonc/mdq223 · 6.58 Impact Factor
  • Molecular Cancer Therapeutics 12/2009; 8(Supplement 1):C213-C213. DOI:10.1158/1535-7163.TARG-09-C213 · 6.11 Impact Factor
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    ABSTRACT: The purpose of this study was to analyze improvements in overall survival over 21 years (1982-2002), with a 5-year minimum follow-up, in the largest series from a single center ever reported. Materials and methods: All diagnoses of high-grade osteosarcoma were included despite histological varieties, age, site and stage. Of the 1656 cases observed, 198 patients were excluded (41 consultation only, 129 low-grade varieties, and 28 lost to follow-up). Within 1458 included patients, 1032 had characteristics to be enrolled in conventional clinical trials (classic histology, age <41, localized, and extremity disease). Data are also analyzed in subgroups to define patients who benefited most. With a median follow-up of 12 years (5-25 years), 754 patients (51.7%) are alive, of whom 613 continuously disease free. Survival at 5, 10, and 15 years is 57%, 52%, and 51%, respectively. Patients candidates for clinical trials have a survival rate of 68%, 64%, and 61%, respectively. Survival for the other patients is 30%, 25%, and 24%, respectively. Trend (joinpoint statistical analysis at real 5-year follow-up) shows a yearly statistically significant improvement of 1.31% (95% confidence interval 0.5% to 2.1%) from 51% for patients treated in 1982 to 68% for those treated in 2002. Patients who statistically benefited were those who relapsed or presented with metastatic disease at diagnosis or had axial tumors. Despite the lack of new drugs for osteosarcoma, survival has statistically improved, especially for those patients with the worst outcome. Aggressive treatments are recommended for all patients including those with poor prognosis.
    Annals of Oncology 11/2009; 21(6):1366-73. DOI:10.1093/annonc/mdp502 · 6.58 Impact Factor
  • Journal de Radiologie 10/2009; 90(10):1459-1459. DOI:10.1016/S0221-0363(09)75715-4 · 0.57 Impact Factor
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    ABSTRACT: A phase 2 trial was carried out to assess the antineoplastic activity of 2 courses of cyclophosphamide-etoposide in relapsed osteosarcoma patients. Twenty-six relapsed osteosarcoma patients with a median age of 18.5 years (8.3-47.1) were enrolled. Seven patients were in first relapse (27%), 11 in second relapse (42%), 7 in third relapse (27%), and 1 in fourth relapse (4%). Eighteen patients had bone metastasis at study entry (69%). Cyclophosphamide was given at 4 g/m(2) on Day 1 followed by etoposide at 200 mg/m(2) on Days 2, 3, and 4. Second cyclophosphamide and etoposide was planned at 21 days to 28 days from the previous one. The primary endpoint of the study was the clinical benefit at 4 months measured as progression-free survival. Progression-free survival at 4 months was 42%. Five patients achieved responses (19%), 9 patients had stable disease (35%), and 12 had tumor progression (46%). Overall survival (OS) at 1 year was 50%. The only grade 4 extrahematological toxicities were fever (5%), acute bronchospasm (4%) and stomatitis (18%). Six patients (23%) underwent radical surgery after cyclophosphamide and etoposide x2. Cyclophosphamide and etoposide x2 may arrest osteosarcoma progression in a significant number of patients (54%). Osteosarcoma progression arrest after cyclophosphamide and etoposide x2 translates in a better OS. Cyclophosphamide and etoposide x2 had good tolerability and the toxicity was time-limited and resolved in all cases.
    Cancer 07/2009; 115(13):2980-7. DOI:10.1002/cncr.24368 · 4.90 Impact Factor
  • S Ferrari, E Palmerini, ME Abate
    Nephrology Reviews 06/2009; 1(6). DOI:10.4081/hmr.v1i6.673
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    ABSTRACT: To determine activity and toxicity of high-dose ifosfamide (HDIFO) in recurrent or advanced Ewing sarcoma family tumors (EFT). Thirty-seven EFT patients [median age 17 years (6-45 years)] previously treated with chemotherapy regimens including standard dose ifosfamide were enrolled. HDIFO was administered for metastatic recurrent disease in 33 patients and for progression during neoadjuvant chemotherapy in 4 patients. All patients who received two courses of 15 g/m(2) ifosfamide were evaluable for radiographic response assessed according to RECIST criteria. Transient Grade 4 neutropenia and thrombocytopenia in 97% and 54% HDIFO courses respectively and severe CNS toxicity in one patient were observed. Thirty-five patients were evaluable: 12 (34%) had complete (2) or partial (10) response, 11 (32%) had stable disease, and 12 (34%) had progression. In patients with relapsed or advanced EFT previously treated with standard dose ifosfamide HDIFO is active and it should be considered a treatment option.
    Pediatric Blood & Cancer 05/2009; 52(5):581-4. DOI:10.1002/pbc.21917 · 2.56 Impact Factor

Publication Stats

2k Citations
500.44 Total Impact Points


  • 2002–2014
    • Istituto Ortopedico Rizzoli
      • Laboratory of Experimental Oncology
      Bolonia, Emilia-Romagna, Italy
  • 2008
    • University of Bologna
      Bolonia, Emilia-Romagna, Italy
  • 1999–2005
    • Policlinico San Matteo Pavia Fondazione IRCCS
      • s.c. Cardiologia
      Ticinum, Lombardy, Italy
  • 2000–2002
    • University of Pavia
      Ticinum, Lombardy, Italy