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Advances in the Treatment of Giant Cell Tumour of Bone

Peter C. Ferguson, M.D., FRCSC
Assistant Professor of Surgery, University of Toronto
Division of Orthopaedic Surgery, Mount Sinai Hospital
Department of Surgical Oncology, Princess Margaret Hospital
Toronto, ON

Giant cell tumour (GCT) of bone is considered a benign aggressive tumour that occurs in the epiphyseal-metaphyseal region of long bones, most commonly the distal femur, proximal tibia and distal radius1. Other less common sites include the proximal humerus, proximal femur, distal tibia and sacrum1. GCT presents as a painful lytic lesion, may have an effusion in the adjacent joint, and may have a soft tissue mass. Approximately 30% of patients with GCT in the lower extremity present with pathologic fractures2 (Figure 1). GCT has a low, but definite risk of metastasis, with lung being the most common site1.

For tumours arising in non-expendable bones such as the femur, tibia and humerus, the mainstay of treatment is intralesional resection. Historically, the rate of local recurrence of GCT has been reported to be high, between 30-50%3-5. In recent years this rate has fallen to between 5-15%, largely due to advances in surgical management and the use of adjuvant therapies2,6,7.

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Figure 1: Coronal CT scan of distal femur showing intra-articular pathologic fracture of medial femoral condyle through giant cell tumour.

 

 

 

 

 

 

 

 

 

 

 

 

The sequence of steps in surgical management of GCT involve curettage to remove all gross tumour, further enlargement of the defect using a high-speed burr to remove microscopic disease, use of adjuvant (if any) and filling of the defect with a material to restore bony integrity. Use of the high-speed burr to deal with microscopic disease is likely responsible for the majority of improvement in local control of GCT. Blackley et al reported a rate of local recurrence of 13% in 61 patients with GCT of long bones using only curettage and a burr, without any adjuvants2. Similar series utilizing a burr without any adjuvants have shown a similarly low recurrence rate8.

Several different adjuvant therapies have been reported to be associated with further improvements in local control of GCT, but these improvements have been marginal. Furthermore, studies reporting use of adjuvants have been retrospective and no randomized controlled trials have been conducted. The most commonly used adjuvant therapies are phenol, ethanol, liquid nitrogen, argon laser cryotherapy, hydrogen peroxide, PMMA cement, and external beam radiation.

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Figure 2: Sagittal CT scan of distal femur pathologic fracture through GCT showing diaplacement of medial femoral condyle and intra-articular step.

 

 

 

 

 

 

 

 

 

 

 

 

Phenol acts by causing chemical necrosis of residual tumour cells. Most studies examining its use fail to demonstrate a significant reduction in local recurrence9-11. One study has demonstrated a local recurrence rate of 6%12 but this study excluded pathologic fractures, which may tend to have a more aggressive clinical course and an associated higher rate of local recurrence. Similarly, the rate of local recurrence with ethanol seems to be similar to that without adjuvants13,14. Cryotherapy, using either liquid nitrogen or argon, causes thermal necrosis. Results with this technology seem to suggest an improvement in local control. Local recurrence with liquid nitrogen15 and argon16,17 are both consistently less than 10%. The main drawback however is a relatively high complication rate including fracture, neuropraxia and wound necrosis15,17. Hydrogen peroxide has been demonstrated to be toxic in vitro to GCT cells8. One study utilizing a combination of hydrogen peroxide, electrocautery, phenol and sterile water has reported a local recurrence rate of 6% suggesting that this combination may be better than no adjuvant18. A promising potential adjuvant is intralesional bisphosphonate therapy. Zolendronate, and to a lesser extent pamidronate, have been demonstrated to cause apoptosis of giant cells in vitro19, and their use should theoretically avoid complications such as tissue necrosis, neuropraxia and fracture. Clinical trials are currently ongoing. External beam radiation has been utilized in situations where patients have had multiple recurrences, where complete surgical resection would detrimentally affect the patient's function, or where complete tumour removal is not possible, such as in the sacrum or spine. In these difficult cases, which are likely pre-selected to have a higher local recurrence rate, low dose external beam radiation results in local control comparable to most other series of extremity lesions20,21.

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Figure 3: Postoperative anteroposterior radiograph showing reconstruction of pathologic fracture with combination of morsellized autograft, bulk allograft and internal fixation.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Cement has been widely mentioned as an adjuvant as the heat of polymerization was thought to cause thermal necrosis of any remaining viable tumour cells. This, however, does not appear to be the case. A large retrospective study, comparing patients from multiple centres with and without cement, failed to demonstrate a significant reduction in local recurrence rate in the cement group7. The main benefit of cement in filling the defect is that it allows immediate weight-bearing as the cement has immediate strength and therefore the patient's function returns to normal at an earlier stage. This is in comparison to bone grafting with a combination of autograft and allograft, which requires internal fixation to provide stability and develops maximal strength after many months of bone remodeling. Final functional outcomes, however, are comparable between the two groups7. Another reported advantage of cement is earlier detection of local recurrence at the cement bone interface.

The advantage of bone graft is that it is biologic and that bone stock is restored. This can be important in the situation of a patient who develops late osteoarthritis as a more conventional total knee arthroplasty can then be performed. If osteoarthritis develops after use of cement, which is the case more often than in patients with bone grafting22, the issue of bone stock becomes a major concern and a megaprosthesis or bulk allografting may be necessary. Bone graft may also be advantageous to promote healing in the setting of pathologic fracture (Figures 1-3).

Local control of GCT, although much improved compared with treatment methods 20 years ago, continues to pose a challenge in a small group of patients. Use of adjuvants such as argon cryotherapy and hydrogen peroxide and perhaps agents specifically toxic to GCT cells such as bisphosphonates, may further improve local control and reduce the morbidity in this group of patients, who otherwise have an overall excellent oncologic prognosis. Prospective multi-centre randomized trials should be encouraged to attempt to establish the benefit of adjuvant therapies.

References

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