Malignant peripheral nerve sheath tumours (MPNSTs) constitute 10% of soft tissue sarcomas. A significant proportion arise in neurofibromatosis type 1 (NF1). Several publications have compared MPNST survival in sporadic and NF1 patients, without consensus on whether NF1 is an independent factor for poor prognosis.

Clinical and histological data from 135 proven MPNSTs were analysed from 2 national centres for soft tissue tumour surgery diagnosed from 1979 to 2000. 129 patients had follow-up data from 6 months to 21 years. 35 were from patients with NF1. Local treatment involved surgery in surgery in 95%, radiotherapy in 44% and chemotherapy in 21%.

NF1 patients were younger than those with sporadic tumours (median age 26 years vs 53 years, p< 0. 001). Overall MPNST survival was almost identical to that in soft tissue sarcomas as a whole, but was worse in NF1 than in sporadic tumours (33% vs 72% at 30 months [p< 0. 01], 17% vs 39% at 60 months, 6% vs 21% at 120 months). A trend towards shorter time to local recurrence was seen in NF1, but not time to metastasis. Superficial tumours gave improved prognosis. Tumour volume over 100ml was associated with worse survival (46% vs 91% at 30 months, p< 0. 02), as was histological grade (80% high grade vs 25% low grade at 60 months, p< 0. 01). In terms of location, a non-significant over-representation of NF1 MPNSTs in the sciatic and brachial plexii was identified.

NF1 and sporadic MPNSTs exhibited no difference in depth or tumour volume profile, although NF1 tended towards higher grade. Analysis of survival in only high grade tumours, however, still resulted in a significant survival disadvantage in NF1 (33% vs 70% at 30 months, p< 0. 01). Removal of brachial and sciatic plexus tumours from analysis did not affect survivorship profiles in NF1 and sporadic MPNSTs.

Grade, volume and tumour depth correlate with survival; only 7 of 45 patients with deep high grade tumours over 100ml volume were observed to survive beyond 2 years. MPNST survival is worse in NF1 than sporadic tumours. Grade, depth, site and volume differences could not explain this disadvantage.

Few studies of wound complications following limb salvage surgery for soft tissue sarcomas separate anatomical compartments. Forty-nine patients with adductor compartment sarcomas underwent limb salvage surgery, 43% developing significant wound complications, 25% requiring further surgery and 20% had delays in adjuvant radiotherapy as a result. Prior surgery by non tumour surgeons and previous radiotherapy led to an increased risk of wound healing problems. In this particular group of patients, special attention should be made to prevent wound healing complications, possibly involving plastic surgeons at an earlier stage of management.

Between 1982 and 1997, twenty-six children between the age of 2 and 15 (mean age 10. 6 years) underwent proximal femoral replacement. Twenty have survived and all but three have reached skeletal maturity.

Sequential radiographs have been reviewed with particular reference to acetabular development and fixation of the prostheses. Initially a cemented acetabular component was inserted, but recently uncemented implants and unipolar femoral heads that exactly fit the acetabulum have been used.

In older children the acetabulum develops normally and the components remain well fixed. One of nine children over thirteen years with a cemented acetabulum needed revision for loosening and one suffered recurrent dislocations.

In younger children the acetabulum continues to develop at the triradiate cartilage, so a cemented acetabulum grows away from the ischiopubic bar. As the component is fixed proximally, it becomes increasingly vertical and will almost inevitably loosen. In our study six of eight children under 13 years of age with a cemented acetabulum needed revision for loosening.

Unipolar replacements in younger children tend to erode the superior acetabular margin. Femoral head cover is difficult to maintain, and of four unipolar implants in children under thirteen, two required acetabular augmentation.

Cemented cups may be unsuitable for children under thirteen years but our results are not statistically significant. In this age group, unipolar implants may be more appropriate but they have serious potential complications. In children over thirteen, cemented implants survive longer. The number of uncemented implants in our study is too small to comment on long-term survival.

To assess whether primary spindle cell sarcomas of bone behave like other primary bone sarcomas.

185 patients with primary spindle cell sarcomas of bone, that is non-osteosarcoma, non-chondrosarcoma and non-Ewings sarcoma of bone, were identified from the patient database of the Orthopaedic Oncology Service in Birmingham, UK. This database contains information on over 10, 000 patients treated in Birmingham since 1970 and collected prospectively since 1986.

Spindle cell sarcomas of bone are primary bone tumours which share the histological spindle shaped cells. They are a heterogeneous group including the cytological diagnoses of malignant fibrous histiocytoma (MFH), spindle cell sarcoma, leiomyosarcoma, fibrosarcoma, angiosarcoma and secondary sarcoma.

119 (64%) of the patients were male. The mean age was 47 years with 116 (63%) older than 40 years. Only 6 patients were low grade and 34 had metastases at presentation. 12 patients developed tumours secondarily to other pathology such as Pagets or radiotherapy. The patient’s limb was affected in 155 (84%) of cases with the distal femur being the most common site.

Treatment was with chemotherapy and surgery where indicated. Chemotherapy was with adriamycin and cis-platin most commonly and was neoadjuvant in 75% of those who had it. Of the 150 patients who had surgery, 113 (75%) had limb salvage.

Overall five year survival was 52 %. Survival in patients who had high grade limb tumours, with no metastases at presentation and which weren’t secondary tumours had a five year survival of 60 %. These results are comparable to previous studies looking at similar tumour groups. Good prognostic factors included treatment since 1980, good response (> 90% necrosis) to neo-adjuvant chemotherapy, limb tumours, age < 40 and local control. 73% of patients with local recurrence died with a mean survival of 11 months. There was no difference in outcome or behaviour between the different diagnoses although prognosis was slightly better than those of aged matched patients with osteosarcoma.

Spindle cell sarcomas of bone respond in a similar way to, if not better than, osteosarcoma when treated in the same way with chemotherapy and surgery. Consequently this should be the preferred method of management.

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.

Reconstruction of the shoulder joint following resection of the proximal humerus for bone tumours remains controversial. We report the long term functional results of the simplest form of reconstruction – an endoprosthesis.

One hundred patients underwent endoprosthetic replacement of the proximal humerus between 1976 and 1998. Thirty eight had osteosarcoma, 17 had chondrosarcoma, 16 had metastases and 9 had Ewing’s sarcoma. Mean age was 36 years (range 10 to 80 yrs). Survivorship of patients and prostheses were calculated. Function was assessed using the Musculoskeletal tumour society (MSTS) and Toronto extremity salvage (TESS) scoring systems. Thirty patients could come to the clinics for MSTS scoring and 38 out of 49 alive patients replied to the TESS questionnaires sent out to them.

The overall survival of the patients was 42% at 10 years. Local recurrence (LR) arose in 16 patients, being most common in chondrosarcoma (26%) and osteosarcoma (22%) and arose in 50% of patients with these tumours who had marginal excisions. Of these 16 patients, 8 had forequarter amputations whilst the remainder had excisions and radiotherapy. Mean time to LR was 12 months and all but two of these 16 patients subsequently died within a mean of 18 months.

The prostheses proved reliable and dependable. Only 9 required further surgery of any sort, 2 needing minor surgery to correct subluxation and 7 needing revisions, one for infection after radiotherapy and six for loosening – three after trauma. The survivorship of the prosthesis without any further surgery was 86. 5% at 20years. The survivorship of the limb without amputation was 93% at 20 years.

The functional outcome was very predictable. Most patients had only 45 degrees of abduction although three patients had normal movements. The mean MSTS functional score was 79% and the mean TESS score was also 79%. There was a high level of patient satisfaction but difficulty was encountered especially in lifting and in all activities above shoulder height. Endoprosthetic replacement of the proximal humerus is a predictable procedure providing reasonable function of the arm below shoulder height. The endoprostheses have proved highly dependable with a low re-operation rate. There is a high risk of local recurrence after inadequate surgery which should be avoided if possible.

This retrospective clinical study describes our experience of the use of growing endoprostheses in children with primary malignant tumours of the proximal femur and analyses the results.

Between 1983 and 1996 we treated nine children with primary bone tumors of the proximal femur by resection and proximal femoral extensible replacements. Outcomes measured were function of the limb using Musculoskeletal Tumor Society score, oncologic outcome, complications and equalization of limb length. Results: Four patients died as a result of pulmonary metastases. The remaining five patients were observed for an average follow-up period of 7. 6 years (range 11–12. 7 years). One patient had a hindquarter amputation for uncontrolled infection. In these five patients we performed an average of 10. 2 operative procedures per patient (range of 3–17 procedures) including 5 lengthening procedures (range of 1–8 procedures) and a mean total extension of 69. 7 mm per patient. Acetabular loosening and hip dislocations were the most frequent complications. Only two patients have not had a revision or a major complication. Despite this, 4 children are alive with a functioning lower limb and a mean Musculoskeletal Tumour Society functional score of 77. 6%. The limb length discrepancy was less than 1 0 mm in three of these patients. The remaining patient has a discrepancy of 50 mm and is awaiting further limb equalization procedures.

Extendible endoprostheses of the proximal femur in selected children is a viable reconstructive procedure. It allows for equalization of limb length and the ability to walk without the use of mobility aids.

34 two-stage revision procedures were carried out between 1989 and 1998 for controlling deep infection following resection of bone tumours and reconstruction with endoprostheses. In 4 cases the procedure failed with early recurrent infection. In six others infection reappeared after further operative procedures. Six of these ten patients required amputation. The success of the procedure in controlling infection was 75% at 5 years. Two stage revision procedures have proved effective in controlling infection in massive endoprostheses but the risk of re-infection appears to be much greater in patients requiring further surgery for any cause.

Although pathological fractures in the aged are usually due to metastasis, solitary lesions with undetected primary should be treated with caution. Assumption of such lesions as metastatic and their subsequent internal fixation could lead to completely inappropriate treatment if the lesion turns out to be a primary sarcoma of bone.

Referrals to our bone tumour service over a four year period were analysed. There were 62 pathological fractures of which 11(17. 8%) were primary sarcomas that were treated as a metastasis. The limb salvage was compromised and survival rates poor in these group.

Although it is believed that primary sarcomas are rare in the aged, our database confirms that 14% of primary sarcomas affect this age group. The survival figures of primary sarcomas in the aged (> 60 years) treated at our centre was a mean of 43 months with a 5-year survival of 22%. The presence of a pathological fracture did not significantly alter the long-term survival of these patients. On the other hand, metastasis had a poor survival with a mean of 19 months and a 5-year survival of 4% showing a significant difference. In addition, these patients underwent major inappropriate surgeries, which rendered limb-salvage difficult, worsened the morbidity and caused mental distress to patients.

Any pathological fracture in the aged presenting as a solitary osseous lesion with an undetected primary or even remote primary should be treated with caution. Their diagnosis needs to be established by biopsy whatever the age of the patient before any form of internal fixation is undertaken. The temptation to carry out biopsy and internal fixation at the same sitting or even a prophylactic fixation should be avoided when the diagnosis is not clear. Standard principles of musculoskeletal oncology need to be followed.

Local recurrence (LR) following treatment of a sarcoma is generally accepted to be a poor prognostic sign and an indicator both of inadequate local control as well as of the failure of adjuvant treatment.

Of 2589 patients with non metastatic Ewings, osteo-sarcoma, chondrosarcoma or a soft tissue sarcoma, 316 have developed LR at some stage following initial treatment of their tumour. 120 were already known to have metastases elsewhere when they developed LR or were found to have them at time of restaging but 196 developed LR as the first sign of relapse.

The mean time to development of LR was 24 months and 72% had arisen within the first two years. Overall survival following LR was 25% at 5 years and 20% at 10 yrs. In patients with metastases at the time of LR or who were found to have them at the time of restaging the median survival was 6 months with only 12% being alive at 2 years. In those with LR as first sign of relapse median survival was 3 years with 30% long term survivors. Patients with low grade tumours had a better outcome than those with high grade – 50% being cured by further surgery. Of the high grade tumours without metastases at time of diagnosis relapsed Ewing’s had the worst prognosis with median survival of 8 months compared with 22 months for osteosarcoma, 36 months for STS and 36 months for chondrosarcoma, despite which overall survival was 16% for both Ewing’s and osteo-sarcoma patients but was 30% for chondrosarcoma and STS.

LR following sarcoma surgery is due to a combination of aggressive disease with inadequate surgery and ineffective adjuvant treatment. In isolated LR aggressive further treatment is justified with an outcome similar to that of metastatic disease.

Survival in the wake of hindquarter amputation and oncological treatment is improving; the hindquarter amputee population is increasing. Some amputees function well, others do not. To assess quality of life and function of hindquarter amputees.

21 amputees (10 females and 11 males) consented to take part in the study. Ethics approval was sought. Assessment was performed using postal questionnaires; SF36 for quality of life; TESS (Toronto Extremity Salvage Score) for physical function and mobility; IEFF( International Index for Erectile Function) for male sexual function; a prosthetics questionnaire to assess prosthetic use.

Mean age of the group was 55 with the mean survival of 7 years post amputation.

Quality of life results were compared to normal subjects and patients for long term illness. Amputees had a significant reduction in quality of life concerning physical function and pain. Social function, mental health and energy levels were equivalent to patients with long term illness.

The mean TESS result was 56.9 with females having a mean score of 61.7 and male of 48. 50% of the group considered themselves as severely to completely disabled; 50% considered themselves moderately disabled. Five were in full time employment.

Six males responded to the sexual function questionnaire. Impotence was universally experienced.

Only five amputees used their prosthesis regularly. All amputees have experienced and 20 continue to experience phantom pain.

This study illustrates that hind quarter amputees have poor physical function and a low quality of life. Phantom pain is universally experienced. Male amputees experience impotence. Addressing these areas would improve the life of current and future hind quarter amputees.

Due to advances in the assessment and treatment of patients with metastatic bone disease, the survival has improved in recent years.

It was the aim of this met-analysis to assess the outcome of patients with metastatic bone disease across Europe.

Five major bone tumour treatment centres participated in the met-analyses. Data had been collected prospectively and was retrieved from the databases for the purpose of this study. All patients were referred to the bone tumour centre for assessment and possible surgical treatment.

The data of almost 2500 patients were analysed. The average age at diagnosis was 60 years and the male to female ratio was 1:1.07.

The overall 5-year survival was 35%, but this was significantly better in metastatic disease of the thyroid and breast as well as multiple myeloma.

The number and site of metastases or the presence of a pathological fracture were not prognostic factors in terms of survival. Patients who were female or younger than 50 years of age at time of diagnosis had a better outcome.

This registry will be expanded and more information analysed to try and provide useful information about prognostic factors and outcome for patients with meta-static bone disease.

We studied 55 patients with stage-IIB osteosarcoma around the knee with respect to the expression of matrix metalloproteinase (MMP)-9 in the surviving tumour cells in surgical resection specimens. They were followed up for a minimum of 2.5 years.

Factors significantly associated with poor overall survival were a high serum level of alkaline phosphatase at diagnosis and tumour cells expressing MMP-9 in the resection specimens. The only factor strongly associated with disease-free survival was the immunohistochemical status of tumour cells for MMP-9 in the resection specimens. The percentage of necrosis after chemotherapy failed marginally to reach statistical significance. On Cox regression analysis only MMP-9 remained significant for overall and disease-free survival.

From the European Osteosarcoma Intergroup study 202 patients were assessed with respect to their surgical treatment. Although treated in three different centres the survival of the three groups was identical (57% at five years). Two of the centres had rates of limb salvage of 85% and 83%, respectively, while the third had a rate of 49%. The corresponding risks of local recurrence were 13.3%, 6.8% and 2.5%, with all local recurrences arising in limbs with attempted limb salvage. Local recurrence was closely related to the adequacy of the margins of excision and to the chemotherapeutic response. Patients who had undergone limb-salvage surgery and who developed local recurrence still survival at five years). Of patients who relapsed, 31% of those with local recurrence alone were cured by further treatment, as compared with only 10% of those with metastases. Limb-salvage surgery with effective chemotherapy remains the optimum treatment for osteosarcoma.

We studied 153 patients with non-metastatic chondrosarcoma of bone to determine the risk factors for survival and local tumour control. The minimum follow-up was for five years; 52 patients had axial and 101 appendicular tumours. Surgical treatment was by amputation in 27 and limb-preserving surgery in 126.

The cumulative rate of survival of all patients, at 10 and 15 years, was 70% and 63%, respectively; 40 patients developed a local recurrence between 3 and 87 months after surgery and 49 developed metastases. Local recurrence was associated with poor survival in patients with concomitant metastases but not in those without.

On multivariate analysis independent risk factors for rates of survival include extracompartmental spread, development of local recurrence and high histological grade. Independent risk factors for local recurrence include inadequate surgical margins and tumour size greater than 10 cm. Location within the body, the type of surgery and the duration of symptoms are of no prognostic significance. Surgical excision with an oncologically wide margin provides the best prospect both for cure and local control in these patients.

Limb salvage is now customary in the treatment of primary bone tumours. The proximal tibia is a frequent site for these neoplasms but reconstruction, especially in children, is a formidable challenge. We reviewed 20 children with extendible replacements of the proximal tibia, all with a minimum follow-up of five years. Five died from their disease and, of the remaining 15, four had above-knee amputations for complications. Infection occurred in seven patients; in five it was related to the lengthening procedure. Aseptic loosening is inevitable in the younger children and only two have avoided a revision, amputation or other major complication; both were aged 12 years at the time of the initial surgery. Despite this, 11 children are alive with a functioning leg and a mean Musculoskeletal Tumour Society functional score of 83%. The lengthening mechanisms used in our series required extensive open operations. We are now using a simpler, minimally invasive, technique which we hope will decrease the incidence of complications. At present, the use of extendible prostheses of the proximal tibia remains an experimental procedure.

We carried out excision of a solitary bony metastasis from renal-cell carcinoma in 25 patients in the hope that this would produce a prolonged disease-free interval. Two patients had excisions only, five had amputations and 18 had excision and endoprosthetic replacement. The one-, three- and five-year cumulative survival rates were 88%, 54% and 13%, respectively.

There were three complications. One patient developed a local recurrence and three had problems related to the endoprosthesis.

We recommend radical excision of a solitary bony metastasis from renal-cell carcinoma to achieve local control of the tumour for the remainder of the patient’s life.

Dedifferentiated chondrosarcoma is a rare, highly malignant variant of chondrosarcoma in which a high-grade spindle-cell sarcoma coexists with a lower-grade chondroid tumour. We have reviewed our experience with this neoplasm in 22 patients, all of whom were treated using modern oncological principles of planned resection and chemotherapy. Despite this the median survival was under nine months and only 18% were alive at five years. Those patients who received chemotherapy, and in whom wide margins of excision were achieved at operation, did best. It is essential to have an accurate preoperative diagnosis in order to plan treatment which may offer a better prospect of cure.

Over a 25-year period we have treated 36 patients with osteosarcoma of the pelvis. Of the tumours, 24 (67%) were primary osteosarcomas and 12 (33%) arose either after irradiation or in association with Paget’s disease. Six patients had a hindquarter amputation and 12 were treated by a limb-salvage procedure with intrapelvic excision.

The five-year survival rate of all the patients with pelvic osteosarcoma was 18%, while for 17 treated by chemotherapy and surgery it was 41%. The prognosis for patients presenting with metastases or with secondary osteosarcoma was appalling and none survived after 29 months. No patient over the age of 50 years when seen initially survived for a year. Youth and a good response to chemotherapy along with complete surgical excision offer the best chance of cure.