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Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XIV | Pages 63 - 63
1 Apr 2012
Ruggieri P Montalti M Pala E Calabrò T Guerra G Fabbri N Ferrari S Picci P Mercuri M
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Aim

Patients treated with limb salvage surgery for bone sarcomas of the extremities (upper and lower) may have physical disability as a result of treatment. Goal of this study was to evaluate the quality of life after treatment (chemotherapy and conservative surgery) at long term.

Method

208 patients resected for a bone sarcoma and with prosthetic reconstruction (45 in the upper and 163 in the lower limb) were evaluated. Assessment of results was done using the Karnofsky Scale (K.S.). Patients were followed in the clinic and functional results assessed according to the Musculoskeletal Tumour Society (MSTS) system. Moreover the Toronto Extremity Salvage Score questionnaire (TESS) was mailed to 144 patients.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XIV | Pages 23 - 23
1 Apr 2012
Bovée J Meijer D Szuhai K van den Akker B de Jong D Krenacs T Athanasou N Flanagan A Picci P Daugaard S Liegl-Atzwanger B Hogendoorn P Bovée J
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Besides conventional chondrosarcoma, several rare chondrosarcoma subtypes are described, comprising about 15% of all chondrosarcomas. Clear cell chondrosarcoma (CCS) is a low-grade malignant tumour, often recurring after curettage, and showing overall survival of about 85%. Mesenchymal chondrosarcoma (MCS) is a highly malignant tumour occurring in bone and soft tissue of relatively young patients. The tumour shows differentiated cartilage mixed with undifferentiated small round cells. It often metastasises and shows a 5-year overall survival of 55%. Dedifferentiated chondrosarcoma (DDCS) is a tumour containing a high-grade non-cartilaginous sarcoma (DD), and a usually low-grade malignant cartilage-forming tumour (WD).

The prognosis is poor. The lack of efficacious treatment of these rare tumours emphasises the need to learn more about their characteristics and to unravel potential targets for therapy.

We constructed tissue microarrays (TMAs) with 2mm cores of 45 DDCS (WD and DD), 24 CCS, and 25 MCS, in triplicate.

Using immunohistochemistry, we investigated protein expression of estrogen-signaling molecules, growth plate-signaling molecules, and other molecules which might be potential targets for therapy. In addition, we gathered genomic information using Agilent 44K oligo arrays.

30% of the WD components were positive for Cox-2. Almost all others were negative. For Bcl2, 88% of the small cells and 32% of the cartilage in MCS were positive. In CCS, WD, and DD 48%, 4%, and 12% were positive, respectively. We demonstrated the presence of ESR1 and aromatase protein in the majority of tumours in all subtypes. Using array CGH, we observed similar aberrations in the two components of DDCS, with additional aberrations in the DD.

Celecoxib treatment is not recommended, as most of the tumours are negative for Cox-2. However, the presence of ESR1 and aromatase support a possible effect of anti-estrogen treatment in all subtypes, and application of Bcl2 inhibitors might chemosensitise MCS.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XIV | Pages 56 - 56
1 Apr 2012
Ferrari S Serra M Longhi A Alberghini M Ruggieri P Palmerini E Staals E Mercuri M Abate M Picci P
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Prognostic stratification of patients with non-metastatic osteosarcoma may improve the clinical management and the design of clinical trials.

Data from 773 patients [median age 15 years (3-40)] treated at our Institute from 1983 to 2000 with high-dose methotrexate, cisplatin, doxorubicin and ifosfamide (neoadjuvant chemotherapy) were analyzed. After multivariate analysis including age, site, tumour volume (cut-off 200 mL), serum LDH and Alkaline Phosphatase (SAP), histology (osteoblastic and chondroblastic vs others), high LDH and SAP, osteoblastic and chondroblastic histotypes resulted independent prognostic factors of DFS.

Patients were grouped according to a score from 0 (absence) to 3 (one to 3 adverse factors). The scoring system was implemented by the addition of PgP expression and grade of chemotherapy-induced necrosis.

A score of 0, 1, 2, 3 was given to 14%, 38%, 32% and 16% of patients respectively.10-year DFS was 80% (95%CI 72-89) for score of 0, 58% (95%CI 52-64) for 1, 53% (95%CI 46-59) for 2 and 40% (95%CI 32-50) for 3 (p= 0.001). PgP expression (168 patients) identified patients with 100% probability of DFS (score of 0 and negative PgP) and patients with 18% (95%CI 52-64) DFS (score of 3 and positive PgP).

Good (GR) and poor responder (PR) patients had the same probability of DFS in case of score of 0 [GR82% (95% CI 72-91), PR79% (95% CI 65-93)] and score of 3 [GR43% (95% CI 32-55) PR36% (95% CI 21-51)]. Different probability of DFS in case of score of 1 [GR64% (95% CI 57-72) PR47% (95% CI 36-59)] and score of 2 [GR63% (95% CI 55-71) PR36% (95% CI 21-51)].

It is possible to stratify outcomes of patients with non metastatic osteosarcoma of the extremity by means of a simple score based on easily available clinical parameters. This scoring system is worth to be validated on larger series.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XIV | Pages 65 - 65
1 Apr 2012
Fabbri N Tiwari A Umer M Vanel D Alberghini M Ruggieri P Ferrari S Picci P Mercuri M
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Aim

Purpose of this study was to review a single Institution experience and results of management of extraskeletal osteosarcoma (OGS), with emphasis on the role of combined treatment consisting of surgery and adjuvant chemotherapy.

Method

Retrospective study of 48 patients observed 1966- 2007 was undertaken: 36 patients were managed at our Institution while 12 cases were consultations and not included in this study. Clinico-pathologic features and details of treatment of all 36 patients were correlated with outcome. Updated follow-up was available in all patients.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XIV | Pages 59 - 59
1 Apr 2012
Picci P Sieberova G Alberghini M Vanel D Hogendoorn P Mercuri M
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Aim

To report late development of sarcomas on sites of previously curetted and grafted benign tumours. Rare cases of development of sarcomas in sites of previous benign lesions are documented, and the development is generally considered secondary to progression of benign lesions, even without radiotherapy.

Methods and Results

In our files, 12 cases curetted and grafted, without radiotherapy addition developed sarcomas from 6 to 28 years from curettage (median 18). Age at first diagnosis (9 GCT, 1 benign fibrous histiocytoma, ABC and solitary bone cyst) ranged from 13 to 55 (median 30). For all cases radiographic and clinic documentation was available. Histology was available for 7 of the benign lesions and for all malignant lesions. The type of bone used to fill cavities was autoplastic in 4 cases, homoplastic in 2 cases, homoplastic and tricalciumphosphate/hydrossiapatite in 1 case, autoplastic and homoplastic in 1 cases, heteroplastic in 1 case. In 3 cases the origin was not reported. Secondary sarcomas, all high grade, were 8 OS, 3 MFH, and 1 fibrosarcoma.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_I | Pages 76 - 76
1 Jan 2011
Gibbons CLMH Jones F Taylor R Knowles H Hogendoorn P Wass JAH Balke M Picci P Gebert C Athanasou NA
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Introduction: Giant cell tumour of bone (GCTB) is an expansile osteolytic tumour of bone which contains numerous osteoclast-like giant cells. GCTB is a locally aggressive tumour which can cause extensive bone destruction that can be difficult to control surgically, up to 35% of cases recurring after simple curettage. Bisphosphonates are anti-resorptive agents that have proved effective in the treatment of a number of osteolytic conditions.

Methods: This study reports results from four European centres where bisphosphonates are being used to treat problematic GCTBs. Details of treatment with bisphosphonates of 25 cases of primary, recurrent and metastatic GCTBs was assessed clinically and radiologically.

Results: Most primary/recurrent tumours did not exhibit progressive enlargement and, in some cases, both primary and metastatic GCTBs showed a degree of radiological improvement following treatment. Some patients also noted relief of pain following treatment. In a few cases, no apparent treatment effect was noted and there was disease progression. Several inoperable large spinal/pelvic GCTBs remained stable in size following treatment.

Discussion: Our findings provide preliminary evidence for the use of bisphosphonates to inhibit the progressive osteolysis associated with GCTB. These agents had a beneficial clinical and/or radiological effect in most cases. This study reports results from four European centres and highlights the fact that these centres are all employing different clinical indications and different regimes of bisphosphonate treatment. Bisphosphonates have significant side effects and indications for treatment and standardisation of drug type and dosage regimes (and measurement of agreed outcome measures to determine treatment efficacy) should be established for the use of these agents to control GCTB tumour growth and osteolysis.


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. 92-B, Issue SUPP_III | Pages 442 - 442
1 Jul 2010
Verbeke S Fletcher C Picci P Daugaard S Kroon H Hogendoorn P Bovée J
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Haemangiopericytoma (HPC) was first described by Murray and Stout as a soft tissue neoplasm with distinct morphologic features, presumably composed of pericytes. Over the years, it became clear that many tumours could mimic a HPC-like pattern. These days, it is accepted that in soft tissue most lesions diagnosed as HPC in the past are actually solitary fibrous tumours (SFT), synovial sarcomas (SS) or myofibromatoses. It has been unclear whether the very rare HPC of bone is atrue entity, or that the HPC-like vessels are non-specific and part of other, different entities.

We collected 10 primary HPC of bone from four institutions diagnosed between 1952 and 2002. All data were reviewed. Immunohistochemistry was performed for CD31, CD34, factor VIII, SMA, keratin AE1/AE3 and EMA. Staining was evaluated as focal positive, diffuse positive or negative.

There were five female and five male patients between 21 and 73 years of age (mean 45.3 y). All tumors were located within bone. The primary site of the tumour was the femur in two patients, humerus in one, fibula in one, sacrum in two and vertebra in three. All tumours showed the presence of prominent thin-walled branching vessels surrounded by more undifferentiated spindle or round cells. However these cells showed some variation in their morphologic pattern: five tumours showed a patternless architecture and varying cellularity, consistent with SFT. Three tumours showed more densely packed sheets of poorly differentiated cells, similar to SS, and one case each represented paraganglioma and PEComa, possibly metastatic. Tumours resembling SFT showed usually focal to diffuse staining for CD34. All tumours were negative for SMA. Two tumours more similar to SS showed focal positive staining for keratin AE1/AE3 or EMA (66%). Some tumours showed severe decalcification artefact. None of the 10 tumours show CD31 and factor VIII expression. FISH is performed to study SYT rearrangements.

Our retrospective review of tumours diagnosed as HPC of bone in the past revealed the absence of true pericytic differentiation and the existence of both SFT of bone and SS of bone. Therefore, as in soft tissue tumours, HPC-like features are non specific. Diffuse CD34 staining is helpful to diagnose SFT of bone, whereas keratin/EMA staining is suggestive for SS of bone.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 438 - 438
1 Jul 2010
Ferrari S Smeland S Bielack S Comandone A Dileo P Picci P Hall KS Eriksson M Honegger H Reichardt P
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EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.) is the first prospective multicenter international study for patients 41–65 year old with high-grade bone sarcoma

Patients with HG Osteosarcoma (OS), HG sarcoma NOS (S), Fibrosarcoma, MFH, Leiomyosarcoma, Dedifferentiated Chondrosarcoma (DCh) were included. Chemotherapy: Combinations of cisplatin/doxorubicin (CDP 100mg/m2/ADM 60mg/m2), ifosfamide/CDP(IFO 6g/m2/CDP 100mg/m2) and IFO/ADM (IFO 6g/m2/ADM 60mg/m2) were repeated three times (9 cycles). Surgery was planned after 3 cycles. Methotrexate (8g/m2) was postoperatively added in poor responders. Immediate surgery was allowed and 9 cycles with CDP, ADM, IFO were postoperatively given.

At December 2007, 140 patients were registered (median age 51 years). OS (51%), S (16%), and DCh (11%) were the more frequent histotypes. Synchronous metastases in 30 (21%) patients, central location of tumor in 45(32%).Surgical complete remission (SCR) was achieved in 84% of patients, (localized 91%, meta-static 37%) without difference among the histology groups. One surgical-related and one chemotherapy-related death were reported.

Grade4 WBC and PLT incidence was 55% and 17%.Renal toxicity and peripheral neurotoxicity were reported in 16% and 20% of patients. With a median follow-up of 25 months (4–68) 3 year OS was 58% (95%CI 48–68%) [7% (95%CI 0–19%) without SCR]. In patients with SCR, 3-year OS and EFS were 46% (95%CI 9–83%) and 0% in case of synchronous metastases and 69% (95%CI58–80%) and 45% (95%CI33–57%) for localized patients; 50% (95%CI 29–71%) and 40% (95%CI 20–59%) for patients with central tumor, 73% (95%CI61–85%) and 44% (95%CI31–57%) for those with extremity tumor; 68% (95%CI 52–83%) and 46% (95%CI 32–54%) for OS, 64% (95%CI 42–85%) and 48% (95%CI 25–71%) for S, 48% (95%CI 13–82%) and 27% (95%CI 1–54%) for DCh.

The protocol is feasible, but the chemotherapy-related toxicity is remarkable. Surgical complete remission is the main factor influencing survival. Central location and synchronous metastases are negative prognostic factors, but 50% 3-year OS can be achieved with aggressive local and systemic treatment. Osteosarcoma and high-grade sarcoma NOS benefit from chemotherapy more than patients with dedifferentiated chondrosarcoma.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 443 - 443
1 Jul 2010
Alberghini M Kliskey K Krenacs T Picci P Athanasou NA
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Giant cell tumour of bone (GCTB) is a primary tumour of bone characterised by a proliferation of mononuclear stromal cells and infiltrating macrophages and osteoclast-like giant cells. GCTB has a variable and unpredictable course and can produce metastatic lesions, mostly in the lungs, in up to 3% of cases. Whether these represent tumour implants rather than true neoplastic secondaries is uncertain. In this study, we analysed morphological and immunophenotypic features of primary GCTBs which metastasised to the lung as well as the metastatic lesions themselves in order to determine if these would provide a clue as to the mechanism of lung metastasis in GCTB.

17 cases of primary GCTB which metastasised to the lung and the lung metastases in these cases were obtained from IOR, Bologna. Morphologically, primary tumours showed variable features, often containing both giant cell-rich and mononuclear stromal cell-rich areas. Mononuclear cells showed frequent mitotic activity and a degree of nuclear pleomorphism; none of the tumours showed cytological features of malignancy. The tumours were highly vascular and frequently contained dilated thin-walled blood vessels and large areas of haemorrhage. GCTB lung metastases were generally small and contained osteoclast-like giant cells and mononuclear stromal cells which showed typical mitotic activity; cytologically, the metastatic tumours were relatively bland and showed little nuclear pleomorphism. Expression of HLA-DR (an allele of which has been associated with a more aggressive GCTB phenotype) and smooth muscle actin (SMA) was noted in stromal cells in primary and secondary GCTBs; frequently, the same pattern of SMA expression was seen in both primary and secondary lesions. Osteoclasts were vitronectin receptor+, CD14-HLA-DR- in both primary and secondary GCTBs.

Our findings indicate that mononuclear stromal cells in lung metastases of GCTB often recapitulate the immunophenotype of the primary tumours from which they derive. Taken with the morphological finding that many primary GCTBs are highly vascular and contain areas of haemorrhage, it is possible that the lung “secondaries” of GCTB more likely represent tumour implants than true neoplastic metastases.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 439 - 439
1 Jul 2010
Alberghini M Ruggieri P Angelini A Ussia G Gambarotti M Ferrari C Vanel D Picci P Mercuri M
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Forty-six hemangioendotheliomas (HE) of bone treated at Rizzoli from 1985 to 2004 were studied with minimum follow up of 4 years: 19 females and 27 males, mean age 37 years, mean follow-up 9 years, 35 cases unifocal at diagnosis (10 spine – 1 with lung metastasis also- 11 lower limb, 8 upper limb, 6 pelvis) and 11 with multifocal involvement. In 10 patients intralesional surgery was previously performed elsewhere. In 27 patients primarily treated at Rizzoli with unifocal localization, surgery was used in 15 cases, surgery and radiotherapy in 7, surgery with radio/chemotherapy in 1 and no surgery in 4 (2 radiotherapy, 1 radio/chemotherapy and 1 embolization). Eight unifocal patients already treated elsewhere had surgery in 3 cases, surgery and radiotherapy in 3, surgery with radio/chemotherapy in 1 and surgery plus chemotherapy in 1. Three of the unifocal cases had further bone involvement subsequently. Nine multifocal patients primarily treated at Rizzoli had surgery in 4 cases, surgery and radiotherapy in 4, surgery with radio/chemotherapy in 1. The 2 previously treated multifocal HE had 1 surgery and 1 radiotherapy.

Six patients died: 3 of disease, 1 of radio-induced osteosarcoma, 2 of different disease. Two patients are AWD. Of remaining 40 patients, 26 are NED (mean follow up 9 years), 11 NED after treatment of recurrence, 1 NED after treatment of radio-induced sarcoma. No lung metastases were diagnosed after treatment. All 10 cases previously treated intralesionally had recurrence. Two of 15 unifocal cases treated with surgery recurred (13%). None of 9 resected unifocal cases previously untreated recurred. Two of 21 pts. with radiotherapy (9.5%) had radio-induced sarcoma.

Surgery is recommended, resection when feasible. Radiotherapy, implying risk of induced sarcoma, should be reserved to multifocal or unresectable cases. Adverse prognostic factor was previous intralesional surgery.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 434 - 435
1 Jul 2010
Panchwagh Y Fabbri N Serra M Ferrari S Picci P Mercuri M
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Osteosarcoma is the most common second malignancy seen in retinoblastoma survivors. Risk of developing osteosarcoma in this group is estimated approximately 500 times higher than the general population. Prognosis in this setting has been reported significantly worse than conventional osteosarcoma despite multimodal management. Purpose of this study was to evaluate clinical features, molecular aspects and outcome of treatment in this subgroup of osteosarcoma patients.

Between 1985 and 2004, from a total of about 1100 osteosarcomas, 7 survivors of retinoblastoma developing high-grade osteosarcoma as second malignancy presented at the authors’ Institution. Retrospective study was undertaken to analyze presentation, tissue expression of RB1, P53, PGP and DHFR, treatment and outcome of both retinoblastoma and osteosarcoma.

Retinoblastoma was bilateral in 5 cases and unilateral in two. All the patients had been treated with a combination of surgery +/− chemotherapy +/− radiation.

None of them had evidence of retinoblastoma at the time of second malignancy diagnosis. Average age at diagnosis of osteosarcoma was 14 years (9–17 years), mean interval between the two malignancies was 155 months. All the osteosarcomas were in the appendicular skeleton, all but one around the knee. Molecular analysis showed defective RB1 gene in all cases All the seven patients received contemporary multimodal management for osteosarcoma. All but one patient died of osteosarcoma within 30 months from diagnosis. The living patient had local recurrence 9 years after limb salvage and is currently disease free following amputation.

Prognosis of osteosarcoma in retinoblastoma patients remains poor as compared to conventional high grade osteosarcoma despite multimodal management. No obvious correlation was found between poor prognosis and P53, PGP and DHFR expression.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 191 - 191
1 Mar 2006
Fabbri N Sangiorgi L Maini V Campanacci L Pedrini E Mercuri M Picci P
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Multiple Hereditary Exostoses is a rare skeletal chondrodysplasia characterized by the presence of a variable number of osteochondromas, usually mostly affecting the long bones but possibly located anywhere. Appearance and growth of exostoses is parallel to the patient’s growth, essentially ending when skeletal maturity is reached.

Its clinical expression is well known and may vary from asymptomatic to severe deformities and is rarely complicated by trasformation to secondary chondrosarcoma (0.5–2%). Research in the field of genetics has lead to identification of 2 responsible genes, EXT1 and EXT2, located respectively on chromosome 8 and 11, both coding for transmembrane glycoproteins involved in the synthesis of heparan-sulfate chains.

A third rare abnormality (EXT3) has been located on chromosome 19 but the responsible gene has not been identified yet.

Seems logical to investigate the genetic basis of the disease and the correlation with clinical aspects, either severity of the deformities and consequent functional impairment and potential for chondrosarcoma.

At the authors’ Institution a total of 550 patients with Multiple Hereditary Exostoses are presently filed. Genetic screening by DHPLC (Denaturing High Performance Liquid Chromatography) and clinicoradiographic orthopedic evaluation has been carried out on 200 patients. So far, 45 mutations have been identified (35 in EXT1 and 10 in EXT2) in 167 patients, 20 of which presented with negative family history and are therefore considered “de-novo” mutations.

Comparison of the clinical data and prospective long term follow-up will possibly clarify different prognosis and risk of secondary chondrosarcoma for different genotypes.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_II | Pages 112 - 112
1 Feb 2003
Ford S Saithna A Grimer RJ Picci P
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Current survival rates for cancer in the UK are perceived to be worse than those in mainland Europe. In order to asses this we investigated the prognostic value of patient and treatment parameters in the management of osteosarcoma, and whether these parameters are equally important across international boundaries.

Retrospective, cross-sectional study of patients (n=428) diagnosed with non metastatic distal femur or proximal tibia osteosarcoma, between 1990–1997 at two specialist orthopaedic oncology centres; Birmingham, UK and Bologna, Italy. Disease free survival (DFS) and overall survival (OS) were assessed by Kaplan-Meier, Fisher’s PLSD and Cox proportional hazard regression. Results : DFS and OS were 43% and 60% at 5 years in Centre 1 and 56% and 73% at Centre 2 respectively. Median survival was 108 weeks at Centre 1 and 136 weeks at Centre 2. A significant difference in DFS and OS was demonstrated between the centres (p=0. 0019 and p=0. 0280 respectively). The most important prognosticators were raised alkaline phosphatase (p=0. 002 and p=0. 0019), degree of chemotherapy induced necrosis (p=0. 0001 and p=0. 0002) and tumour volume > 150cm³ (p=0. 0037 and p=0. 0057).

The most significant combination of prognosticators was alkaline phosphatase and tumour necrosis. 75% of patients in centre 2 had a good chemotherapy response (> 90% necrosis) compared to only 29% in Centre 1. The other prognostic indicators were evenly matched. Chemotherapy regime was found to have significantly different outcome in DFS and OS.

This is a retrospective study designed to explore possible reasons for differences in survival between two international centres. It would appear that all known patient factors were matched between the centres but that the main difference was in the effectiveness of chemotherapy. Further international prospective studies are needed to confirm these findings.