S Ferrari

Istituto Ortopedico Rizzoli, Bolonia, Emilia-Romagna, Italy

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Publications (140)502.56 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: 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 patients. This study aimed to explore the role of miR-34A expression on prognosis of Ewing sarcoma patients.
    Annals of Oncology 07/2014; · 7.38 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; · 7.38 Impact Factor
  • American Journal of Clinical Oncology 03/2013; · 2.55 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; · 7.38 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. · 7.38 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. · 7.38 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).
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    ABSTRACT: To evaluate the role of enbloc resection on the oncological outcome of patients with Ewing's sarcoma of the mobile spine treated with systemic multiagent chemotherapy combined with radiation therapy. While the role of chemotherapy and radiation therapy is well known and accepted in the treatment of Ewing sarcoma, there is no consensus on the role of enbloc resection in those tumors occurring in the mobile spine and, therefore, it can be difficult to conclude the decision making process, particularly if to achieve a tumor-free margin resection functionally relevant structures should be sacrificed. The study design of this work was the retrospective analysis of a series of 27 cases of Ewing sarcoma of the mobile spine homogeneously treated. Twenty-seven patients with primary ES of the mobile spine were treated from 1979 to 2008 by the same multidisciplinary team. All the patients presented with pain. Motor deficits were present in 6 patients. All the patients were submitted to multiagent protocols of chemotherapy (always) and radiotherapy (alternative to surgery or associated to). Surgery was performed in 17 cases both for functional purpose (7 cases: intralesional piecemeal excision) both for curative purpose (10 cases: enbloc resection, resulting characterized by marginal/wide or intralesional margins). Patients were observed for a minimum of 2 years or until death. The mean follow-up time was 65 months (median 28 months; ranging 2 to 218 months). Neurological function, local recurrence, distant relapse, and treatment-related complications were evaluated. Three periods were considered according to the evolution of therapeutic strategies. Four patients were treated in the period 1979 to 1982. All were submitted to chemotherapy (REA-2) and radiation therapy (RT). Two of them were submitted to intralesional excision. All these patients died 2 to 29 months later without significant difference in the two groups. In the period 1983 to 1990 all patients were treated with chemotherapy (REN-1/2) and RT. Two were submitted to intralesional excision and had a worse evolution as died of the disease at 2 and 11 months follow up, while the patients who did not received surgery evolved more favourably: 1 died of the disease 57 months after the end of the treatment, 3 are continuously disease free at 130, 190, 290 months. The sixteen patients treated in the period 1991 to 2008 received chemotherapy (REN-3 and ISG-SSG) and RT, combined with intralesional excision in 3, with enbloc with intralesional margins in 4, enbloc with tumor-free margins (wide or marginal) in 6. Only one patient submitted to tumor-free margin enbloc resection had local recurrence and died 29 months after the treatment (biopsy was performed by open approach), the other surviving continuously disease free at 17 to 193 months follow-up (av. 76 months). All the patients submitted to intralesional excision and to enbloc resection resulting in margin violation had the same prognosis, as died of the disease 10 to 63 months after the treatment. Only one of the 3 patients who had no surgery died of the disease 8 months after the treatment, the other surviving 9 and 49 months follow-up. Among the seven patients who had neurological symptoms at the occurrence, just those with no metastasis and who underwent enbloc resection are alive. The current study seems to demonstrate that tumor-free margin enbloc resection provides better local control and longer survival, while the results after intralesional margin resection or piecemeal excision combined with chemotherapy and RT is less effective than chemotherapy and RT alone.
    European review for medical and pharmacological sciences 07/2011; 15(7):831-9. · 1.09 Impact Factor
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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. · 7.38 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. · 7.38 Impact Factor
  • Radiotherapy and Oncology - RADIOTHER ONCOL. 01/2011; 99.
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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. · 0.83 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. · 7.38 Impact Factor
  • Annals of Oncology 05/2010; 21 Suppl 5:v204-13. · 7.38 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. · 7.38 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 06/2009; 115(13):2980-7. · 5.20 Impact Factor
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    ABSTRACT: The influence of age and sex on chemotherapy-related toxicity was evaluated in children and adults with non metastatic osteosarcoma. treatment consisted of methotrexate (MTX, 12 g/m(2)), cisplatin (CDP 120 mg/m(2)) and doxorubicin (ADM 75-90 mg/m(2)) and high-dose ifosfamide (HDIFO). toxicity data from 1,051 courses (295 with MTX, 756 based on doxorubicin, cisplatin and high-dose ifosfamide) were analyzed. Children (4-14 yrs) and females showed a higher incidence of grade 4 neutropenia and thrombocytopenia and were more frequently hospitalized for neutropenic fever compared to adolescents and young adults (AYA, 15-19 yrs) and adults (>20-40 yrs). Delayed MTX excretion was higher in adults than AYA and children. Adults (up to 40 years) can be treated with pediatric protocols for osteosarcoma and they experience lower hematologic toxicity compared to pediatric population. further investigations on sex-related susceptibility to chemotherapy in osteosarcoma patients are recommended.
    Journal of chemotherapy (Florence, Italy) 04/2009; 21(2):205-10. · 0.83 Impact Factor
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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 02/2009; 52(5):581-4. · 2.35 Impact Factor
  • Journal De Radiologie - J RADIOL. 01/2009; 90(10):1459-1459.
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    ABSTRACT: The 'leave me alone' bone lesions are very classical, and, as indicated by their name, do not require any further investigation. There are very typical cases, and there are also more difficult ones, and they can be especially difficult to manage if the patient has a known cancer.
    Cancer Imaging 01/2009; 9 Spec No A:S38-43. · 1.59 Impact Factor

Publication Stats

2k Citations
502.56 Total Impact Points

Institutions

  • 1992–2014
    • Istituto Ortopedico Rizzoli
      • Laboratory of Experimental Oncology
      Bolonia, Emilia-Romagna, Italy
  • 2012
    • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
      Milano, Lombardy, Italy
  • 2008
    • University of Bologna
      Bolonia, Emilia-Romagna, Italy
  • 1999–2005
    • Policlinico San Matteo Pavia Fondazione IRCCS
      Ticinum, Lombardy, Italy
  • 2000
    • University of Pavia
      Ticinum, Lombardy, Italy