What is the management approach for Giant Cell Tumors?

Management Approach for Giant Cell Tumors of Bone (GCTB)

Surgery is the treatment of choice for resectable Giant Cell Tumors of Bone, with en bloc excision for high-risk tumors and intralesional curettage with adjuvants for carefully selected cases. 1

Initial Assessment and Diagnosis

• All patients with suspected GCTB should be managed by a bone sarcoma multidisciplinary team 1
• Exclude brown tumors of hyperparathyroidism with serum calcium levels 1
• Confirm diagnosis with histopathology, looking for characteristic giant cells and H3F3A gene mutation detection 1
• Assess tumor location, size, soft tissue extension, and proximity to critical structures

Treatment Algorithm

1. Surgical Management (Primary Treatment)

For Resectable Tumors:

• En bloc excision 1:

  • Indicated for tumors with extensive bone destruction
  • When joint preservation is impossible
  • For expendable sites (e.g., fibular head)
  • Lower recurrence rate (5% vs 25% with intralesional surgery) 2

• Intralesional curettage with adjuvants 1:

  • For carefully selected cases where joint preservation is possible
  • Better functional outcomes than wide resection 3
  • Adjuvants to improve local control:
    • High-speed burring 1
    • Cement filling (polymethylmethacrylate) - reduces recurrence compared to bone grafting 2
    • Cryotherapy 1
    • Other options: phenol, hydrogen peroxide, zinc chloride 4, 5

2. Medical Management

Denosumab (monoclonal antibody to RANKL) 1:

• Standard treatment for:

  • Unresectable GCTB 1
  • Metastatic GCTB 1
  • Cases where surgery would cause unacceptable morbidity 1

• Administration protocol:

  • Monthly subcutaneous injection after three weekly loading doses 1
  • All patients require daily calcium and vitamin D supplements 1
  • Adequate contraception must be used to avoid pregnancy 1

• Preoperative (neoadjuvant) use:

  • Can solidify soft tissue component to facilitate surgical resection 1
  • May reduce risk of recurrence 1
  • Should be individualized and reserved for complex cases 1
  • Complete resection usually preferred after denosumab treatment 1
  • Note: Curettage after denosumab can be difficult and has higher recurrence risk 1

3. Radiation Therapy

• Can provide local control but associated with risk of transformation to high-grade sarcoma 1
• Limited to cases where:
  • Surgery leads to unacceptable morbidity 1
  • Denosumab is ineffective or contraindicated 1

4. Management of Metastatic Disease

• Patients with metastatic disease may require long-term denosumab treatment 1
• For stable disease after two years of treatment, dosing interval can be extended from 4-weekly to 8-weekly 1
• Surgery for pulmonary metastases is usually not performed 1

5. Management of Malignant Transformation

• Rarely, GCTs can transform to high-grade malignant tumors 1
• These do not benefit from denosumab 1
• Treat with combination cytotoxic chemotherapy following protocols for osteosarcoma 1

Follow-up Protocol

• Physical examination of the tumor site
• Assessment of function and complications of reconstruction
• Local imaging and chest X-ray/CT
• For high-grade tumors: every 3-4 months for first 2-3 years, then every 6 months for years 4-5, then yearly 1
• For low-grade tumors: every 6 months for 5 years, then annually 1

Prognostic Factors and Recurrence Risk

• Soft tissue extension is the most relevant prognostic factor for recurrence 1
• En bloc excision has lower recurrence rates than intralesional curettage (5% vs 25%) 2
• Use of polymethylmethacrylate (cement) decreases recurrence risk compared to bone grafting 2
• Up to 5% of GCTBs metastasize to the lungs, often maintaining benign morphology 1
• Transformation to high-grade malignancy occurs in 1-3% of cases 1

Special Considerations

• For skull base GCTs, preoperative denosumab can reduce tumor size to a resectable level 6
• Long-term consequences of denosumab treatment, particularly in younger patients, remain unclear 1
• Monitor for denosumab side effects, including osteonecrosis of the jaw and atypical fractures 1

The choice of surgical approach should balance the morbidity of treatment against the risk of recurrence, with preservation of function being a key consideration in the management of these typically benign but locally aggressive tumors.