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The Bone & Joint Journal
Vol. 95-B, Issue 3 | Pages 411 - 418
1 Mar 2013
Nakamura T Grimer RJ Gaston CL Watanuki M Sudo A Jeys L

The aim of this study was to determine whether the level of circulating C-reactive protein (CRP) before treatment predicted overall disease-specific survival and local tumour control in patients with a sarcoma of bone.

We retrospectively reviewed 318 patients who presented with a primary sarcoma of bone between 2003 and 2010. Those who presented with metastases and/or local recurrence were excluded.

Elevated CRP levels were seen in 84 patients before treatment; these patients had a poorer disease-specific survival (57% at five years) than patients with a normal CRP (79% at five years) (p < 0.0001). They were also less likely to be free of recurrence (71% at five years) than patients with a normal CRP (79% at five years) (p = 0.04). Multivariate analysis showed the pre-operative CRP level to be an independent predictor of survival and local control. Patients with a Ewing’s sarcoma or chondrosarcoma who had an elevated CRP before their treatment started had a significantly poorer disease-specific survival than patients with a normal CRP (p = 0.02 and p < 0.0001, respectively). Patients with a conventional osteosarcoma and a raised CRP were at an increased risk of poorer local control.

We recommend that CRP levels are measured routinely in patients with a suspected sarcoma of bone as a further prognostic indicator of survival.

Cite this article: Bone Joint J 2013;95-B:411–18.


The Bone & Joint Journal
Vol. 95-B, Issue 1 | Pages 127 - 131
1 Jan 2013
Grimer RJ Chandrasekar CR Carter SR Abudu A Tillman RM Jeys L

A total of 157 hindquarter amputations were carried out in our institution during the last 30 years. We have investigated the reasons why this procedure is still required and the outcome. This operation was used as treatment for 13% of all pelvic bone sarcomas. It was curative in 140 and palliative in 17, usually to relieve pain. There were 90 primary procedures (57%) with the remaining 67 following the failure of previous operations to control the disease locally. The indication for amputation in primary disease was for large tumours for which limb-salvage surgery was no longer feasible. The peri-operative mortality was 1.3% (n = 2) and major complications of wound healing or infection arose in 71 (45%) patients. The survival at five years after hindquarter amputation with the intent to cure was 45%, and at ten years 38%. Local recurrence occurred in 23 patients (15%). Phantom pain was a significant problem, and only 20% used their prosthesis regularly. Functional scores were a mean of 57%. With careful patient selection the oncological results and functional outcomes of hindquarter amputation justify its continued use.

Cite this article: Bone Joint J 2013;95-B:127–31.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 9 | Pages 1282 - 1287
1 Sep 2012
Mottard S Grimer RJ Abudu A Carter SR Tillman RM Jeys L Spooner D

The purpose of this study was to assess the outcome of 15 patients (mean age 13.6 years (7 to 25)) with a primary sarcoma of the tibial diaphysis who had undergone excision of the affected segment that was then irradiated (90 Gy) and reimplanted with an ipsilateral vascularised fibular graft within it.

The mean follow-up was 57 months (22 to 99). The mean time to full weight-bearing was 23 weeks (9 to 57) and to complete radiological union 42.1 weeks (33 to 55). Of the 15 patients, seven required a further operation, four to obtain skin cover. The mean Musculoskeletal Society Tumor Society functional score at final follow-up was 27 out of 30 once union was complete. The functional results were comparable with those of allograft reconstruction and had a similar rate of complication.

We believe this to be a satisfactory method of biological reconstruction of the tibial diaphysis in selected patients.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXX | Pages 13 - 13
1 Jul 2012
Grimer R Carter S Tillman R Abudu A Jeys L
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Aim

To estimate the risk of bone malignancy arising in premalignant conditions.

Methods

There are quite a number of possible premalignant conditions with considerable uncertainty about the actual risk of a bone sarcoma developing. The incidence of these malignant conditions was identified from a prospective database containing 3000 primary bone sarcomas.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXX | Pages 21 - 21
1 Jul 2012
Bhumbra R Hanna S Jeys L Briggs T Grimer R
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It is generally accepted that there is a high rate of local recurrence following surgical excision of chordoma of the sacrum, even if the margins of excision appear clear. There is uncertainty as to whether the addition of postoperative radiotherapy may decrease the risk of local recurrence, particularly if there are close or involved margins. We aimed to determine the effect of conventional radiotherapy, in the post-operative setting, on the effect of local recurrence, metastases and patient survival in a multi-centre study.

Methods

57 patients were identified from the combined databases of the RNOH and ROH, who underwent surgical excision of a primary sacral chordoma and who had a minimum of three years follow-up.

Results

There were 17 women and 40 men, with a median age of 64 (25-81 range). Median tumour length was 10cm (2-20 range). 22 of the 57 patients died. Survival was 60% at 5 years and 45% at ten years. 28 of the 57 patients developed local recurrence (49%) and margins of excision did not affect the rates of local recurrence.

Adjuvant radiotherapy was used in 9 patients, to with intra-lesional resections, five marginal and two wide. Without radiotherapy the local recurrence rate was 45% at five years. With radiotherapy, the local recurrence rate was 62.5% at five years. There were no statistically significant differences between the two.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXX | Pages 22 - 22
1 Jul 2012
Wafa H Grimer R Carter S Tillman R Abudu A Jeys L
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Introduction

The aim of this study is to evaluate the functional and oncological outcome of extracorporeally irradiated autografts as a method of pelvic reconstruction after internal hemipelvectomy.

Methods

The study included fifteen patients with primary malignant bone tumours of the pelvis. There were 10 males and 5 females with a mean age of 21.5 years (range, 8 to 46 years). Six patients had Ewing's sarcoma, six osteosarcoma, and three chondrosarcoma.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXX | Pages 38 - 38
1 Jul 2012
Bhumbra R Carter S Jeys L Tillman R Abudu A Sumathi V Grimer R
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Osteosarcomas represent a heterogeneous group of primary bone tumours that affect predominantly the long bones of patients in the first two decades of life. We aim to describe the secondary effects of a poor response (⋋90% necrosis) to chemotherapy on the effectivity of other treatment outcomes, local recurrence and survival rates.

182 cases of osteosarcoma with necrosis of less than 90% and no metastases at diagnosis have been seen at our institution over 24 years. There were 60 amputations. 122 patients underwent limb salvage, with 105 marginal margins and 17 contaminated. There was no difference in size or location between the two groups. In the 122 patients with LSS, 21 had adjuvant radiotherapy and 101 did not. In the entirety of patients with ⋋90% necrosis, survival was 64% at 2 years and 37% at 5 years. When LSS Marginal resections were compared with amputation there was a significant (P=0.006) difference in survival. LSS with a marginal margin had a 25% risk of LR. In these patients there was 25% survival, whereas the absence of a local recurrence, conferred a benefit of a 40% survival XRT was used in 21 of the 122 who underwent limb salvage. The decision to use XRT was made by the local oncologist at the treating unit. There was a 24% rate of recurrence in the XRT group and 25% with no XRT.

These data demonstrated that patients who had a poor response to chemotherapy and underwent an amputation faired poorly when compared to patients with LSS. There is a selection bias in patients selected to undergo amputation. Additionally, patients who underwent amputation had a lower rate of local recurrence, but still had a poorer survival when compared to LSS.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXX | Pages 5 - 5
1 Jul 2012
Gaston C Bhumbra R Watanuki M Abudu A Carter S Jeys L Tillman R Grimer R
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Introduction

The role of adjuvants in curettage for giant cell tumours (GCT) is still controversial. Our aim was to determine if adjuvant cementation lowers local recurrence (LR) rates for GCTs treated with curettage.

Methods

Detailed curettage has been the principal treatment for GCT for the past 30 years. Cement was used from 1996 onwards for tumours where there was concern about structural stability. We investigated factors affecting LR and also the incidence of complications for treatment with or without cement.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXX | Pages 9 - 9
1 Jul 2012
Potter R Grimer R Carter S Tillman R Abudu A Jeys L Unwin P
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Aim

To investigate the effectiveness of silver coated prostheses in preventing periprosthetic infection in a high-risk group.

Methods

We have used silver coated prostheses in 48 endoprosthetic replacements in whom there would be a high expected risk of infection.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXX | Pages 36 - 36
1 Jul 2012
Jeys L Darbyshire A Grimer R Tillman R Abudu A Carter S
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Introduction

Myxofibrosarcoma is described by WHO as comprising of a spectrum of malignant fibroblastic lesions with variably myxoid stoma, pleomorphism and with a distinctively curvilinear vascular pattern. They are reported to be one of the commonest sarcomas of elderly patients. It has previously been reported to have a high rate of locally recurrent disease (50-60%). The aim of the study was to investigate the ROH series of tumours to determine prognostic factors for survival and local recurrence.

Methods

Patients were identified from the ROH database who had been treated with a new presentation of myxofibrosarcoma. The size, grade and depth of the tumour at presentation was noted. Those patients who had suffered local or distal disease relapse or died were highlighted. Analysis was undertaken by Kaplan Meier survival curves for univariate and cox regression for multivariate analysis.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXX | Pages 15 - 15
1 Jul 2012
Bhumbra R Jeys L Gaston L Tillman R Abudu A Carter S Grimer R
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The aim was to identify when primary amputation was used as primary treatment and to describe outcomes in patients managed with modern chemotherapy. A detailed review of the electronic patient records was undertaken. Statistical analysis was performed with univariate analysis using Kaplan-Meier curves and Chi2 testing, whilst multivariate analysis was performed using Cox regression analysis.

There were 354 osteosarcomas. 93 patients presented with metastases and 192 subsequently developed metastases at a mean of 46 months. Amputation was performed as the primary surgical treatment in 101 patients. Endoprosthetic reconstruction was used in 253 patients. Amputation was performed as a secondary procedure on 15 patients.

The 5 and 10 year survival data for all patients, including those with metastatic disease were 60% and 60% for amputation with good chemotherapy response (>89% necrosis), 65% and 63% for limb salvage and good response, 21% and 21% for amputation and poor response (⋋90% necrosis) and 51% and 30% for limb salvage with poor response.

Local recurrence occurred both with amputation (10.8%) or limb salvage (9%), with no significant differences between the two.

Univariate analysis demonstrated that the extent of response to chemotherapy induced necrosis significantly affected survival, whether the patient had an amputation or not.

Whether or not amputation or LSS was used in the surgical management of patients, local recurrence rates where similar between the two groups. Further assessment of chemotherapy-induced necrosis is a key factor in determining subsequent limb salvage or amputation management strategies.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXX | Pages 19 - 19
1 Jul 2012
Jeys L Neepal V Mehra A Sumathi V Grimer R
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Introduction

To look at the effect of width and tissue at surgical margins, together with the use of adjuvant therapy on locally recurrent disease and disease free survival.

Methods

The distance (mm) and tissue has been regularly reported for 5 years, prior to this it was reported as wide, marginal or intra-lesional. It is known from previous studies that 90% of locally recurrent disease for osteosarcoma and Ewing's occurs within 2 years from surgery. Therefore all primary bone sarcomas of the pelvis and appendicular skeleton that underwent surgery between 1/1/2005 and 1/1/2008 were entered, giving at least 2 years follow up. The pathology records were reviewed and the margins and percentage tumour necrosis were recorded. Those patients who had suffered local or distal disease relapse or died were highlighted. Analysis was undertaken by Kaplan Meier survival curves with univariate and multivariate analysis.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXX | Pages 14 - 14
1 Jul 2012
Grimer R Jeys L Carter S Tillman R Abudu A
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Chondrosarcoma of bone is a surgical disease and excision with wide margins is the optimum treatment. Sometimes the size or location of the tumour at the time of diagnosis mean that only a marginal excision can be achieved. The effect of the margin of excision on outcome is investigated.

Method

All patients with newly diagnosed primary chondrosarcoma of bone and without metastases at the time of diagnosis were identified from a prospective database. Their outcome was investigated to assess whether the margin of excision affected outcome.

Results

492 patients were included in the analysis with a mean age of 48. The mean tumour size was 11cm and 59% were male. The 10 year tumour specific survival was 85% for clear cell (N=7) and grade 1 (N=210), 60% for grade 2 (N=180), 47% for grade 3 (N=59) and 16% for dedifferentiated (N=36). The 10 year local recurrence free survival was 86% (clear cell), 73% (grade 1), 67% (grade 2), 36% (grade 3) and 56% dedifferentiated.

Local recurrence was strongly related to older age (p=0.0065), grade (p⋋0.0001) and margins (p⋋0.0001). Patients who developed local recurrence had a 43% survival at 10 years compared with 76% for those who did not (p⋋0.0001). They also had a 49% risk of developing metastases compared to a 17% risk for those without local recurrence (p⋋0.0001). However most of these patients had metastases before developing LR(57%). 16 of 65 patients with local recurrence but no metastases, died due to local progression (usually pelvic or spinal tumours). There was however no relation of the margin of excision to either the risk of developing metastases or survival for any grade of tumour.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XIV | Pages 31 - 31
1 Apr 2012
Mottard S Grimer R Carter S Tillman R Abudu S Jeys L Spooner D
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Aim

To identify factors leading to the success or failure of extracorporeal irradiation and re-implantation of bone (ECIR).

Method

Review of experience of this technique since 1996 documenting successes and failures.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XIV | Pages 37 - 37
1 Apr 2012
Dramis A Grimer R Malizos K Tillman R Abudu A Jeys L Carter S
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Aim

To determine the overall survival of patients with Pelvic Ewing's Sarcoma treated in our unit and to identify prognostic factors in pelvic primaries that could be used to select patients who would most likely benefit from high intensity treatment.

Method

Between 1977 and 2009, 80 male and 66 female patients aged 2 to 60 (mean, 18) years with Pelvic Ewing's Sarcomas were retrospectively reviewed from the Royal Orthopaedic Hospital Oncology Service Registry. Treatments included surgery, radiotherapy, chemotherapy, or any of them in combination. Event-free (from presentation to recurrence) and overall (from presentation to death/latest follow-up) survival rates were calculated using the Kaplan- Meier method.

Influence of various factors (age at diagnosis, gender, tumour site, metastasis at presentation, surgery (and surgical margins), radiotherapy, and type of treatment on survival was assessed using SPSS 14.0 statistical software.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XIV | Pages 64 - 64
1 Apr 2012
Jeys L Grimer R Tillman R Abudu S Carter S
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Introduction

The aim of this study was to investigate the results of a series of cases from a single institution with respect to local disease control and patient survival to determine prognostic factors.

Methods

Electronic patient records were reviewed on all patients with STS between February 1963 and January 2007. 2445 patients had over 30 types of STS. 1639 (67%) had not received any treatment prior to presentation, however, 770 patients (32%) had undergone a previous attempted excision. Survival analyses were done using Kaplan Meier and Cox regression analyses, however, for prognostic factor analysis, only patients presenting without prior treatment were included.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XIV | Pages 6 - 6
1 Apr 2012
Malhas A Grimer RJ Carter S Tillman R Abudu A Jeys L
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Since1986 we have monitored the actual diagnosis of all cases referred to our Unit with the diagnosis of ‘possible primary malignant bone tumour’. We have excluded all patients referred with a known diagnosis of either a benign condition or known to have bone metastases. In most cases the suspected diagnosis was based on X-rays alone, sometimes supported by further imaging.

Method

Retrospective review of a prospective database that was started in 1986 identifying the actual diagnosis.

Results

There were 5922 patients with a confirmed diagnosis over the 23 year time period of this study. 2205 (37%) were found to have a primary malignant bone sarcoma and 1309 (22%) had a benign bone tumour. 992 patients had a general orthopaedic condition (e.g. geode or a vascular necrosis) whilst 303 (5%) had a haematological malignancy and 289 (4.9%) infection. 533 patients (9%) had metastases. There was a similar pattern of frequency of all diagnoses except for metastatic disease and haematologic malignancy at different ages. The incidence of metastases increased from the age of 35 onwards


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XIV | Pages 45 - 45
1 Apr 2012
Grimer R Carter S Tillman R Abudu S Jeys L
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Neoadjuvant chemotherapy for osteosarcoma improves outcomes for the majority, but if the chemotherapy does not work then the dilemma often arises as to whether to do limb salvage with a marginal (or worse) margin of excision or to do an amputation. If limb salvage is carried out with a close margin, does post operative radiotherapy make any difference? This study aims to address these questions.

Method

All patients with limb osteosarcoma, no metastases, a poor response to chemotherapy and either a marginal excision or primary amputation were identified from a prospective database. This group were investigated in terms of overall survival and local control.

Results

There were 182 patients in this category of whom 60 had an amputation, 105 limb salvage with marginal margins and 17 with an intralesional margin. Local recurrence (LR) arose in 41% of those with an intralesional margin, 22% of those with a marginal margin and 13% of those with an amputation. Radiotherapy was used in 21 of the 122 patients and the risk of LR was the same as in those who did not have radiotherapy. Neither age nor sex of the patient, size or site of the tumour affected the risk of LR. The overall survival for this group was 42% at 10 years. The survival was best in those with marginal margins (38%) than those with an amputation (28%) and worst for those with an intralesional margin (20%). Survival was worst in those who did develop LR, but no worse than in those having amputation


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XIV | Pages 50 - 50
1 Apr 2012
Chandrasekar C Grimer R Carter S Tillman R Abudu A Jeys L
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The outcome for patients with Ewing's sarcoma recurrence is poor. Local recurrences occur in 8%-25%of these patients. The aim of the study was to analyze the patients who had a local recurrence to identify factors predicting the local recurrence and if it could be prevented

Methods

A retrospective analysis of 650 patients who had a diagnosis of Ewing's sarcoma treated between 1975 and 2009 at a single institution was performed and 64 patients (10%) who had a local recurrence were identified and analysed.

Results

Fifteen patients had metastases at diagnosis.20 patients had chemotherapy and radiotherapy only while 44 had chemotherapy and surgery +/− post op radiotherapy. Thirteen patients who were suitable for post –operative radiotherapy could not receive the treatment due to various reasons like biological reconstruction. The estimated 5 years survival for the patients was 15%. The risk of local recurrence is higher if the tumour is located in the axial skeleton, treatment with chemotherapy and radiotherapy alone [location and size of the tumour precluding surgery]. The risk of local recurrence is higher if the tumour was in the fibula or radius. One out of three patients who have good response to chemotherapy still went on to develop a LR. The use of biological reconstruction and younger age group often resulted in deferral of post-operative radiotherapy. Location and type of treatment can predict LR. Surgery with clear margins and post-operative radiotherapy given when indicated may reduce the incidence of LR.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XIV | Pages 46 - 46
1 Apr 2012
Jeys L Neepal V Mehra A Grimer R
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Introduction

Recently a great deal of interest has emerged in new techniques for resection of bone tumours, such as the use of computer guided surgery, joint sparing prostheses and epiphysiolysis. However, all the techniques may require narrower margins at resection than the traditional Enneking wide margins. The aim of the study was to look at the effect of width and tissue at surgical margins, together with the use of adjuvant therapy on locally recurrent disease and disease free survival.

Methods

The quality in terms of precise distance (mm) and tissue has been regularly reported by our pathologists for 5 years, prior to this it was reported as wide, marginal or intralesional. It is known from previous studies that 90% of locally recurrent disease for osteosarcoma and Ewings occurs within 2 years from surgery. Therefore all primary bone sarcomas of the pelvis and appendicular skeleton that underwent surgery between 1/1/2005 and 1/1/2008 were entered into the study group, giving at least 2 years follow up. The pathology records were reviewed and the quality of the margins and percentage tumour necrosis were recorded. Those patients who had suffered local or distal disease relapse or died were highlighted. Analysis was undertaken by Kaplan Meier survival curves with univariate and multivariate analysis.