Giant cell tumour of the proximal femur

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1 ONCOLOGY Giant cell tumour of the proximal femur IS JOINT-SPARING MANAGEMENT EVER SUCCESSFUL? A. E. Wijsbek, B. L. Vazquez- Garcia, R. J. Grimer, S. R. Carter, A. A. Abudu, R. M. Tillman, L. Jeys From Royal Orthopaedic Hospital, Birmingham, United Kingdom The purpose of this study was to assess whether the use of a joint-sparing technique such as curettage and grafting was successful in eradicating giant cell tumours of the proximal femur, or whether an alternative strategy was more appropriate. Between 1974 and 2012, 24 patients with a giant cell tumour of the proximal femur were treated primarily at our hospital. Treatment was either joint sparing or joint replacing. Jointsparing treatment was undertaken in ten patients by curettage with or without adjunctive bone graft. Joint replacement was by total hip replacement in nine patients and endoprosthetic replacement in five. All 11 patients who presented with a pathological fracture were treated by replacement. Local recurrence occurred in five patients (21%): two were treated by hip replacement, three by curettage and none with an endoprosthesis. Of the ten patients treated initially by curettage, six had a successful outcome without local recurrence and required no further surgery. Three eventually needed a hip replacement for local recurrence and one an endoprosthetic replacement for mechanical failure. Thus 18 patients had the affected joint replaced and only six (25%) retained their native joint. Overall, 60% of patients without a pathological fracture who were treated with curettage had a successful outcome. Cite this article: Bone Joint J 2014;96-B: A. E. Wijsbek, Medical Student B. L. Vazquez-Garcia, MD, Orthopaedic R. J. Grimer, DSc, FRCS, Professor S. R. Carter, FRCS, A. A. Abudu, FRCS, R. M. Tillman, FRCS, L. Jeys, MSc, FRCS, Royal Orthopaedic Hospital, Bristol Road South, Northfield, Birmingham B31 2AP, UK. Correspondence should be sent to Mr R. J. Grimer; The British Editorial Society of Bone & Joint Surgery doi: / x.96b $2.00 Bone Joint J 2014;96-B: Received 12 February 2013; Accepted after revision 3 October 2013 Giant cell tumour of bone is a rare but aggressive benign tumour that typically develops around the knee in the epiphyseal area of a skeletally mature patient, 1 but can present at a number of other sites. 2 Although it usually arises next to a joint, it can also present in an apophysis such as that of the greater trochanter. 2 The treatment of giant cell tumour remains controversial. There have been case series documenting its outcome after curettage, with or without filling the resultant cavity and with or without adjuvant therapy. 3 Complete excision of the involved area is usually curative, but entails sacrifice of the adjacent joint and requires some form of reconstruction, which may have an unpredictable longterm outcome. 4 Curettage results in a higher rate of local recurrence and potential morbidity from further surgery. 5 A wide variety of adjuvant measures have been reported, but no consensus exists about optimal treatment, although there is some evidence that filling the cavity after curettage with cement reduces the rate of local recurrence. 6,7 Giant cell tumour of the proximal femur (PF) constitutes only 5.5% of all giant cell tumours. 2 The management of a giant cell tumour in this site is not clear, and in many cases depends on the experience of the surgeon and the age of the patient. The viability of the hip after aggressive curettage can be a real problem, especially in younger patients, despite leaving an intact articular surface (Fig. 1). In our experience some patients will present with a pathological fracture of the proximal femur, and most of these will already have significant bone destruction at the time of diagnosis. Although there is a natural wish to try and preserve the hip joint, particularly in younger patients, this may not be possible, and alternatives such as total hip replacement (THR) or proximal femoral endoprosthetic replacement (EPR) may have to be considered. A THR will usually entail only partial excision of the giant cell tumour, with curettage of the remainder, whereas EPR usually facilitates complete removal of all diseased bone Although previous studies have reported reasonable results from treating a giant cell tumour of the proximal femur by replacement (either THR or EPR), 8-10 no single study to date has looked at other options for treatment and their outcomes. The purpose of this study was to assess whether the use of curettage and VOL. 96-B, No. 1, JANUARY

2 128 A. E. WIJSBEK, B. L. VAZQUEZ-GARCIA, R. J. GRIMER, S. R. CARTER, A. A. ABUDU, R. M. TILLMAN, L. JEYS Fig. 1a Fig. 1b Fig. 1c Radiograph (a) and MRI (b) of a giant cell tumour of the left proximal femur in a 23-year-old female patient, with considerable thinning of the cortex and extension of the tumour into the femoral neck, which can be more clearly seen on MRI. Radiograph (c) at six months after curettage and grafting with an ipsilateral non-vascularised fibular graft and morsels of allograft. The patient was fully weight-bearing and there was no sign of local recurrence. bone grafting was successful in eradicating giant cell tumours of the proximal femur, or whether an alternative management strategy was more appropriate. Patients and Methods Patients with a giant cell tumour of the proximal femur were identified from a prospectively compiled database and their records and radiographs were reviewed. Inclusion criteria included those who had undergone their initial treatment at our hospital, and histology that confirmed a giant cell tumour. Patients with a recurrent tumour that had previously been treated elsewhere were excluded, as were patients with a short follow-up. Between 1985 and 2012, 24 patients (15 men and nine women) met our inclusion criteria. Their mean age at diagnosis was 31.5 years (17 to 74). The giant cell tumour involved the femoral head or neck in 13 patients, the apophysis of the greater trochanter in four and the whole of the femoral neck and the greater trochanter in two. The original imaging was no longer available for five patients. A pathological fracture was present at the time of diagnosis in 11 of 24 patients (46%). The mean age of patients who presented with a pathological fracture was 32 years (22 to 53), and of patients who presented without a fracture 31 years (21 to 74). The decision about the best treatment for each patient was made after the diagnosis had been confirmed by biopsy and discussion at a multidisciplinary team meeting. The patient was informed of the available options and the risks and benefits of each, and a treatment plan was then agreed. In general, any patient with a fracture through a giant cell tumour was offered a replacement. If the giant cell tumour was localised to the neck of the femur a cemented THR was usually carried out, with meticulous curettage of any tumour in the greater trochanter and proximal femur. If there was extensive bone destruction that extended down the femoral shaft, an EPR was carried out with en bloc excision of the proximal femur. In younger patients without a fracture, consideration was always given to the option of curettage and bone grafting to try and preserve the hip joint. This usually involved an ipsilateral fibular strut graft and packing of the resultant cavity with cancellous allograft (Fig. 1c). Post-operatively patients who had undergone replacement were allowed to bear weight in the first week. Patients treated by curettage were kept non-weight-bearing until six weeks had elapsed, and were then allowed to bear partial weight until their radiographs showed sufficient consolidation to allow full weight-bearing, which was usually achieved by three months. Initial follow-up with radiographs took place at six weeks, then every three months for the first two years and every six months up to five years. If local recurrence was suspected clinically or radiologically it was investigated by MRI and biopsy. The success of the treatment was assessed in terms of tumour control (assessing local recurrence), hip preservation (assessing the need for further surgery) and functional outcome using the Musculoskeletal Tumor Society (MSTS) score. 11 This score is assessed by the surgeon and assesses function and mobility. A maximum score of 30 is possible for a normal state and the final score is usually expressed as a percentage. Results The mean time to follow-up was 103 months (15 to 300). No patient was lost to follow-up. One patient died from causes unrelated to the giant cell tumour or its treatment. The overall survival was therefore 96%. Of the 11 patients with a pathological fracture, seven underwent THR and four had EPR. Of the 13 without a fracture, one had EPR (owing to the extent of disease), two THE BONE & JOINT JOURNAL

3 GIANT CELL TUMOUR OF THE PROXIMAL FEMUR 129 Table I. Patient demographics (MSTS, Musculoskeletal Tumor Society) Patient Age Gender Fracture Initial treatment * Further treatment * Follow-up (mths) MSTS score 1 21 Female No C C/THR Male Yes THR Male Yes HEMI THR THR Female No C/BG Male No THR THR Male No C THR Male Yes EPRPF Male Yes THR EPRPF Female Yes THR Male No EPRPF Male Yes EPRPF Female No C/BG Male No C/BG C/THR Male Yes EPRPF Male No C Male No C Female No C Male Yes EPRPF Female Yes THR Female No C EPRPF Female No C/BG Male No THR Female Yes THR Male Yes THR Reduction of hip * C, curettage; C/BG, curettage and bone grafting; THR, total hip replacement; EPRPF, endoprosthetic replacement of the proximal femur THR and the other ten, curettage. Of those undergoing curettage, four had a fibular graft with or without cancellous bone grafting: none required any form of internal fixation. No complications were noted during the surgery. Post-operatively five patients developed complications. One patient had a superficial wound infection that was explored and subsequently healed. One patient with an EPR and one with a THR dislocated their prosthesis in the early post-operative period, and both of these were reduced (closed). Two patients had a leg length discrepancy, one of 1.5 cm after a THR and one of 2 cm after curettage with bone grafting. Local recurrence occurred in five patients (21%) within three years of the primary surgery, after a mean of 14.8 months (5 to 31) in two of the nine patients treated by THR (22%) and in three of the ten patients treated by curettage (30%), one of whom had also had a bone graft. None of the five patients treated by EPR had a local recurrence. Further surgery for any reason was required in eight patients including local recurrence in five and mechanical failure in three. Of the local recurrences, three were initially treated by curettage, two had a re-curettage and one an EPR. The two patients treated with re-curettage both ultimately had a THR because of further local recurrence. Two patients initially treated by THR had local recurrence, and both were successfully revised to EPR. Mechanical failure occurred in three cases. In one patient who had been treated by curettage there was no sign of healing of the cavity after three months: the patient underwent THR for persistent pain. Two patients with a THR required revision surgery. One patient whose initial THR had been carried out at the age of 27 years needed revision of the acetabular component after 16 years in situ, while the other, who was 30 years of age at diagnosis, had a hemiarthroplasty revised to a THR after 18 years as a result of erosion of the acetabulum. Of the ten patients without a pathological fracture who were treated by curettage (with or without bone graft), six had a successful outcome (60%): there was no sign of local recurrence and no further surgery was needed. The other four failed, three as a result of local recurrence and one due to mechanical failure. Eventually, 18 patients ended up with a replacement and only six (25%) retained their native hip joint (Table I, Fig. 2). MSTS functional scores were carried out at the time of final clinical review: the mean scores were highest in the group treated with curettage with or without bone grafting, and resembled normal functional scores (29.7; 99% (27% to 30%)). The mean THR scores were 25.7 (86% (17% to 30%)) and for EPR 24.7 (82% (19% to 27%)). Unfortunately, the MSTS scores were not available for three patients (Table I). Discussion The classic treatment for a giant cell tumour is curettage. The use of different adjuvant therapies is still being debated, without a clear solution being found. 12 At present there are no randomised clinical studies that justify the use of any adjuvant, and although various case series have suggested benefit for cement, argon laser, cryotherapy and phenol, this VOL. 96-B, No. 1, JANUARY 2014

4 130 A. E. WIJSBEK, B. L. VAZQUEZ-GARCIA, R. J. GRIMER, S. R. CARTER, A. A. ABUDU, R. M. TILLMAN, L. JEYS Pathological fracture Primary surgery Local recurrence Mechanical failure Final surgery 11 with fracture 13 with no fracture EPR EPR 10 THR Fig GCT PF 9 THR remains controversial. 12,13 Most authors agree that adequate exposure and high-speed burring of the edges of the cavity is beneficial, but in some situations, particularly when the bone is already thin, this can lead to an increased risk of fracture. 8 This is particularly true in the femoral neck, where almost half of the patients in our series presented with a pathological fracture. There remains the difficult management decision as to whether to minimise local recurrence by en bloc resection of the lesion, or to try to preserve the joint using a more conservative approach. En bloc resection followed by reconstruction usually results in a poorer functional outcome and has a greater risk of complications. 14,15 Giant cell tumours of the proximal femur have one of the highest rates of pathological fracture of any site (46% in this series), which in itself may increase the risk of local recurrence. Only one of our patients with a fracture, all of whom were treated by resection followed by either THR or EPR, developed a local recurrence. In our series the greatest risk of recurrence was in those treated by curettage. We used no adjuvant treatment, although a high-speed burr was used when appropriate. In this series there were three local recurrences and one mechanical failure. Although the use of adjuvant may have reduced the risk of local recurrence, it might have increased the risk of failure. Because in most cases the giant cell tumour extends almost to the articular surface of the hip joint, there is usually no residual bone left to permit any form of internal fixation (Fig. 1c), so if curettage is to be used, a structural bone graft has the greatest likelihood of success. Similarly, the use of cement to fill a cavity adjacent to the articular cartilage carries the risk of secondary osteoarthritis. 16 Various methods of treating giant cell tumour of the proximal femur have been advocated. 9 Wide resection reduces the risk of local recurrence but usually requires adjunctive replacement, with its associated potential for * 10C ± BG 3 1 6C ± BG Flow diagram showing the various methods of treatment. Two patients (2*) developed local recurrence after curettage and had a repeat curettage which was unsuccessful and so underwent THR. (GCT, giant cell tumour; PF, proximal femur; EPR, endoprosthetic replacement; THR, total hip replacement; C, curettage; BG, bone grafting.) reduced function. 17 Sakayama 10 recommended that replacement should be avoided if possible, even though there were no local recurrences in four of the ten patients in his group that were treated in this manner. Of the five patients treated with joint preservation, two developed local recurrence (40%) and required a subsequent replacement, which very much reflects our experience. 10 Ultimately, 18 of our 24 patients ultimately had a replacement, and only six (25%) kept their native hip joint. Although many of these prostheses will provide reasonable or even excellent function in the medium term, eventual revision is almost inevitable. 18 One of the main limitations of this study is that the series described has been accrued over 27 years. Giant cell tumour of the proximal femur remains a rare condition. It is likely that surgery will remain the mainstay of treatment, although the advent of drug therapy, in particular denosumab, an inhibitor of receptor activator of nuclear factor kappa-b ligand (RANKL), 19 may yet transform the management of all patients with a giant cell tumour of bone. 20,21 No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. This article was primary edited by A. Ross and first-proof edited by D. Rowley. References 1. Campanacci M, Baldini N, Boriani S, Sudanese A. Giant-cell tumor of bone. J Bone Joint Surg [Am] 1987;69-A: Unni KK, Inwards CY, eds. Dahlin s bone tumours. Sixth ed. Philadelphia: Lippincott Williams & Wilkins, Mankin HJ, Hornicek FJ. Treatment of giant cell tumors with allograft transplants: a 30-year study. Clin Orthop Relat Res 2005;439: Errani C, Ruggieri P, Asenzio MA, et al. Giant cell tumor of the extremity: a review of 349 cases from a single institution. Cancer Treat Rev 2010;36: Gaston CL, Bhumbra R, Watanuki M, et al. Does the addition of cement improve the rate of local recurrence after curettage of giant cell tumours in bone? J Bone Joint Surg [Br] 2011;93-B: Szendröi M. Giant-cell tumour of bone. J Bone Joint Surg [Br] 2004;86-B: Kivioja AH, Blomqvist C, Hietaniemi K, et al. Cement is recommended in intralesional surgery of giant cell tumors: a Scandinavian Sarcoma Group study of 294 patients followed for a median time of 5 years. Acta Orthop 2008;79: Khan SA, Kumar A, Inna P, Bakhshi S, Rastogi S. Endoprosthetic replacement for giant cell tumour of the proximal femur. J Orthop Surg (Hong Kong) 2009;17: Balke M, Ahrens H, Streitbuerger A, et al. Treatment options for recurrent giant cell tumors of bone. J Cancer Res Clin Oncol 2009;135: Sakayama K, Sugawara Y, Kidani T, et al. Diagnostic and therapeutic problems of giant cell tumor in the proximal femur. Arch Orthop Trauma Surg 2007;127: Enneking WF, Dunham W, Gebhardt MC, Malawar M, Pritchard DJ. A system for the functional evaluation of reconstructive procedures after surgical treatment of tumors of the musculoskeletal system. Clin Orthop Relat Res 1993;286: Algawahmed H, Turcotte R, Farrokhyar F, Ghert M. High-speed burring with and without the use of surgical adjuvants in the intralesional management of giant cell tumor of bone: a systematic review and meta-analysis. Sarcoma 2010; Oda Y, Miura H, Tsuneyoshi M, Iwamoto Y. Giant cell tumor of bone: oncological and functional results of long-term follow-up. Jpn J Clin Oncol 1998;28: Niu X, Zhang Q, Hao L, et al. Giant cell tumor of the extremity: retrospective analysis of 621 Chinese patients from one institution. J Bone Joint Surg [Am] 2012;94- A: Chanchairujira K, Jiranantanakorn T, Phimolsarnti R, Asavamongkolkul A, Waikakul S. Factors of local recurrence of giant cell tumor of long bone after treatment: plain radiographs, pathology and surgical procedures. J Med Assoc Thai 2011;94: THE BONE & JOINT JOURNAL

5 GIANT CELL TUMOUR OF THE PROXIMAL FEMUR Xu HR, Niu XH, Zhang Q, Hao L, Ding Y, Li Y. Subchondral bone grafting reduces degenerative change of knee joint in patients of giant cell tumor of bone. Chin Med J (Engl) 2013;126: Klenke FM, Wenger DE, Inwards CY, Rose PS, Sim FH. Giant cell tumor of bone: risk factors for recurrence. Clin Orthop Relat Res 2011;469: Saikia KC, Bhattacharyya TD, Bhuyan SK, et al. Local recurrences after curettage and cementing in long bone giant cell tumor. Indian J Orthop 2011;45: Grimer RJ. Denosumab. Bone Joint ;2: Thomas D, Henshaw R, Skubitz K, et al. Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol 2010;11: Chawla S, Henshaw R, Seeger L, et al. Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant cell tumour of bone: interim analysis of an open-label, parallel-group, phase 2 study. Lancet Oncol 2013;14: VOL. 96-B, No. 1, JANUARY 2014

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