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Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 452 - 452
1 Jul 2010
Longhi A Bacci G Ferrari C Picci P Ferrari S
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Prolonged survival have been reached in the last two decades in patients with Ewing’s sarcoma due to combination of chemotherapy and radiotherapy.

We report the analysis of 493 patients treated according to 4 different protocols in 23 years (Jan1983- Dec 2006).Aim of this study was to evaluate the occurrence of late toxicities as Second Malignant Neoplasms (SMN), Cardiomyopathies and sterility.

Methods: We reviewed our database to find out all those patients aged from 1 to 40 yrs with localized Ewing’s sarcoma who were treated with chemotherapy according to 4 different protocols from 1983 to December 2006. Data were updated at Dec 2008

Results: 493 patients had adequate follow up and meet the eligibility criteria. Median age was 16 yrs (1–40) female/male: 183/310.Median overall survival 69 ms (4–302).220 patients died and 273 are alive. 44 pts received HDCT + PBSCR.Eleven SMN were found : 2 AMLeukemia, 2 parotid adenocarcinoma, 1 melanoma, 1 thyroid cancer and 5 radioinduced osteosarcoma. The interval between Ewing’s sarcoma diagnosis and leukaemia diagnosis was shorter then interval between Ewing’s sarcoma and RT osteosarcoma. Six patients reported a Cardiomyopathy : in 4 cases it was mild and pts are well compensated,2 patients needed heart transplant,. One of these two pts received also a kidney transplant due to chronic renal failure due to previous chemotherapy. Fertility: 17 women became pregnant after chemotherapy, 20 women experienced postTx amenorrea: 7 pts received RT in pelvic area, 9 did HDCT, 3 pts were over 30 yrs old. 9 male became father. 8 male patients did sperm analysis 3 azospermia, 4 oligospermia and 1 normal sperm count. No congenital abnormalities in offsprings were reported.

Conclusions: In this casuistic the Cumulative Risk to have a SMN at 5 yrs is 1.8% and 2.9% at 10 yr. The SMN cumulative incidence in Ewing’s sarcoma seems to be lower then in our previous casistic in osteosarcoma patients (ASCO 2006).


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 135 - 135
1 Mar 2009
Fabbri N Schuster S Toscano A Errani C Mercuri M Bacci G
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Introduction: Secondary sarcomas of bone are a rare group of usually high-grade malignant tumors developing over different pre-existing bone conditions, historically associated with worse prognosis than their primary counterpart. Purpose of this study was to investigate the factors affecting the outcome, with emphasis modern multi-modal management.

Methods: From approximately 30000 bone tumor cases filed at our Institution, 87 patients with secondary sarcoma were identified. Secondary chondrosarcomas were not included and all the patients had an high-grade lesion. Patients were divided in 3 groups: radiation induced sarcomas (29), sarcomas in Paget’s disease (34), and sarcomas in benign lesions (24). Of these patients, 67 were admitted for treatment while 20 were consultations; of the 67 patients admitted, 44 had stage II while 23 had stage III disease. There were 57 males and 30 females, average age was 52. Most common histotype was osteosarcoma (81). Treatment varied from none to combined multimodal management including chemotherapy and surgery.

Results: Cumulative survival is 37% at 10 years. Survival was affected by stage of disease (II=54%, III=0%; p< 0.00005), site (extremities 44%, pelvis-spine 0%; p< 0.00005), inclusion of surgery in the treatment plan (yes 51%, no 0%; p< 0.00005), and type of treatment (combined chemotherapy and surgery 56%, surgery 39%; p=0.07). No differences were noted between the 3 main etiologic groups.

Conclusions: Secondary sarcomas are a rare group malignant tumors with heterogeneous clinical features. While stage and site are still the most relevant prognostic factors, modern multimodal management including neoadjuvant chemotherapy and surgery seems to favourably affect the outcome.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 9 | Pages 1229 - 1233
1 Sep 2007
Bacci G Balladelli A Forni C Longhi A Serra M Fabbri N Alberghini M Ferrari S Benassi MS Picci P

Despite local treatment with systemic chemotherapy in Ewing’s sarcoma family tumours (ESFT), patients with detectable metastases at presentation have a markedly worse prognosis than those with apparently localised disease. We investigated the clinical, pathological and laboratory differences in 888 patients with ESFT, 702 with localised disease and 186 with overt metastases at presentation, seen at our institution between 1983 and 2006.

Multivariate analyses showed that location in the pelvis, a high level of serum lactic dehydrogenase, the presence of fever and a short interval between the onset of symptoms and diagnosis were indicative of metastatic disease. The rate of overt metastases at presentation was 10% without these four risk factors, 22.7% with one, 31.4% with two, and 50% for those with three or four factors. We concluded that in ESFT the site, the serum level of lactic dehydrogenase, fever, and the interval between the onset of symptoms and diagnosis are indicators of tumours having a particularly aggressive metastatic behaviour.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 8 | Pages 1071 - 1075
1 Aug 2006
Bacci G Fabbri N Balladelli A Forni C Palmerini E Picci P

Between 1986 and 2002, 42 patients with synchronous multifocal osteosarcoma were treated with two different protocols of neoadjuvant chemotherapy. When feasible, the primary and secondary tumours were excised as a combined procedure.

After initial chemotherapy 26 patients were excluded from simultaneous excision of all their secondary bone lesions as their disease was too advanced. In 12 patients only isolated excision of the primary lesion was possible. For 16 patients simultaneous operations were conducted to excise the primary and secondary lesions. This involved two supplementary sites in 15 patients and four additional sites in one patient. Of these, 15 attained remission but 12 relapsed and died (11 within two years). Three patients remained disease-free at five, six and 17 years. The histological response to pre-operative chemotherapy of the primary and secondary lesions was concordant in 13 of the 16 patients who underwent simultaneous operations at more than one site.

The prognosis for synchronous multifocal osteosarcoma remains poor despite combined chemotherapy and surgery. The homogeneous histological responses in a large proportion of the primary and secondary lesions implies that synchronous multifocal osteosarcoma tumours are not multicentric in origin, but probably represent bone-to-bone metastases from a single tumour.


The Journal of Bone & Joint Surgery British Volume
Vol. 85-B, Issue 1 | Pages 107 - 114
1 Jan 2003
Bacci G Ferrari S Longhi A Versari M Forni C Donati D Manfrini M Trentani P Barbieri E

The role of radiotherapy and/or surgery in the local treatment of Ewing’s sarcoma has still to be determined. The outcome of Ewing’s sarcoma may differ according to its location and a selection bias towards surgery limits the ability to compare methods of local treatment. We have carried out a retrospective review of 91 consecutive patients treated for non-metastatic Ewing’s sarcoma of the femur. They received chemotherapy according to four different protocols. The primary lesion was treated by surgery alone (54 patients), surgery and radiotherapy (13) and radiotherapy alone (23). One was treated by chemotherapy alone.

At a median follow-up of ten years, 48 patients (53%) remain free from disease, 39 (43%) have relapsed, two (2%) have died from chemotherapeutic toxicity and two (2%) have developed a radio-induced second tumour.

The probability of survival without local recurrence was significantly (p = 0.01) higher in patients who were treated by surgery with or without radiotherapy (88%) than for patients who received radiotherapy alone (59%). The five- and ten-year overall survival rates were 64% and 57%, respectively. Patients who were treated by surgery, with or without radiotherapy, had a five- and ten-year overall survival of 64%. Patients who received only radiotherapy had a five- and ten-year survival of 57% and 44%, respectively.

Our results indicate that in patients with Ewing’s sarcoma of the femur, better local control is achieved by surgical treatment (with or without radiotherapy) compared with the use of radiotherapy alone. Further studies are needed to verify the impact of this strategy on overall survival.


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 1 | Pages 88 - 92
1 Jan 2002
Bacci G Ferrari S Lari S Mercuri M Donati D Longhi A Forni C Bertoni F Versari M Pignotti E

We have studied 560 patients with osteosarcoma of a limb, who had been treated by neoadjuvant chemotherapy, in order to analyse the incidence of local and systemic recurrence according to the type of surgery undertaken. Of these, 465 patients had a limb-salvage procedure and 95 amputation or rotationplasty.

At a median follow-up of 10.5 years there had been 225 recurrences. The five-year disease-free survival and overall survival rates were 60.7% and 68.5%, respectively, with no significant difference between patients undergoing amputation and those undergoing resection. The incidence of local recurrence was the same for patients treated by either amputation or limb salvage and correlated significantly with the margins of surgical excision and the histological response to chemotherapy. The outcome for patients with a local recurrence was significantly worse than for those who had recurrent disease with metastases only.

We conclude that limb-salvage procedures are relatively safe in osteosarcoma treated by neoadjuvant chemotherapy. They should, however, only be performed in institutions where the margins of surgical excision and the histological response to chemotherapy can be accurately assessed. If the margins are inadequate and the histological response to chemotherapy is poor an immediate amputation should be considered.


The Journal of Bone & Joint Surgery British Volume
Vol. 62-B, Issue 1 | Pages 93 - 101
1 Feb 1980
Campanacci M Bacci G Pagani P Giunti A

Fifty-five cases of osteosarcoma of the extremities were treated between 1972 and 1976 by combined surgery and chemotherapy (vincristine, adriamycin and methotrexate in medium doses) for 18 months. The follow-up ranges from 30 to 80 months (mean = 48 months). Twenty-six patients remained free from any evidence of disease, two had local recurrences but no metastases and 27 had metastases (four of these also had local recurrences). In 12 patients, the metastases appeared after the end of chemotherapy. Both metastases and local recurrences were more frequent in patients who had segmental bone resection (7/8) than in those treated by more radical surgery (22/47). Comparison with an "historical" group (94 osteosarcoma patients treated by operation alone in our Institute between 1960 and 1971) showed that the percentage of patients free from evidence of disease was higher in the group who receiving chemotherapy. In addition, the appearance of metastases in this group was delayed (mean = 16 months) as compared with the historical controls (mean = 8 months). On the other hand, after the same kind of operative treatment, the rate of local recurrences and the time of their appearance was almost identical in both groups.


The Journal of Bone & Joint Surgery British Volume
Vol. 60-B, Issue 4 | Pages 567 - 574
1 Nov 1978
Bacci G Campanacci M Pagani P

The results are presented of thirty-seven patients with Ewing's sarcoma; ten were treated by a combination of operation, radiotherapy and cyclic chemotherapy, the remainder by radiotherapy and chemotherapy but without operation. The drugs, vincristine, cyclophosphamide and adriamycin were used in combination and were continued for two years. The follow-up ranged from twelve to sixty-two months. The mortality rate and the incidence of metastases were both markedly lower than in a comparable previous series treated by radiotherapy alone, or by operation plus radiotherapy, but all without chemotherapy. The percentage of local recurrences and of metastases was much higher in the twenty-seven patients who had radiotherapy and adjuvant chemotherapy, than in the ten in whom operation was also performed. It is suggested that on the basis of these results (and on theoretical grounds) treatment should consist of radiotherapy combined with chemotherapy plus, whenever feasible, operative excision of the primary tumour.