What is the treatment approach for bone malignancy?

Treatment Approach for Bone Malignancy

All patients with suspected primary malignant bone tumors must be referred to a specialized bone sarcoma reference center BEFORE biopsy, as these tumors are frequently difficult to recognize and mismanagement can compromise outcomes. 1

Initial Diagnostic Workup

Imaging Protocol

• Plain radiographs in two planes are always the first investigation 1
• MRI of the entire affected bone with adjacent joints is mandatory when malignancy cannot be excluded, as it provides optimal local staging for extremity and pelvic tumors 1
• CT should be reserved for visualizing calcification, periosteal bone formation, cortical destruction, or when diagnostic uncertainty exists 1

Staging Requirements Before Biopsy

Complete staging must include: 1, 2

• Chest imaging (chest radiograph or CT) to detect pulmonary metastases
• Bone scintigraphy to evaluate skeletal metastases
• Laboratory studies: complete blood count, lactate dehydrogenase (LDH), and alkaline phosphatase (ALP)
• Whole-body MRI is sensitive for detecting skeletal metastases in Ewing sarcoma and osteosarcoma 1

Age-Based Diagnostic Considerations

• Patients under 40 years with aggressive, painful bone lesions should be referred to an orthopedic oncologist immediately before further workup due to high risk of primary bone malignancy 1, 2
• Patients over 40 years require evaluation for metastatic disease including chest/abdomen/pelvis CT, bone scan, and mammogram if radiographs are non-diagnostic 1, 2

Biopsy Principles

The biopsy must be performed at the reference center by the surgeon who will perform definitive resection or by a radiologist on the team. 1

Critical biopsy requirements: 1

• Minimize contamination of normal tissues
• Use core needle biopsy (preferably image-guided) as appropriate alternative to open biopsy
• Ensure adequate sampling of representative areas
• Send samples for microbiological culture in all cases
• Interpretation by experienced pathologist with clinical details (tumor site, patient age, radiological differential diagnosis)
• If open biopsy: use longitudinal incision and plan biopsy tract to lie within planned resection bed

Treatment by Tumor Type

Osteosarcoma

Standard treatment combines neoadjuvant chemotherapy, surgical resection, and adjuvant chemotherapy, which has improved survival from 10-20% to over 60% for localized disease. 2

Chemotherapy regimen: 2, 3

• MAP protocol (high-dose methotrexate, doxorubicin, cisplatin) is standard for young patients
• Starting dose: methotrexate 12 g/m² IV as 4-hour infusion at weeks 4,5,6,7,11,12,15,16,29,30,44,45 after surgery
• Leucovorin rescue: 15 mg orally every 6 hours for 10 doses starting 24 hours after methotrexate infusion
• Doxorubicin-cisplatin may be used for patients over 40 years or those intolerant to high-dose methotrexate

Ewing Sarcoma

Treatment includes VAC/IE chemotherapy (vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide and etoposide) combined with surgical resection when possible. 4, 2

• Radiotherapy alone should be applied if complete surgical excision is impossible 2
• Survival rates approach 70% for localized disease 1

Chondrosarcoma

Chondrosarcoma is chemoresistant; surgery is the primary treatment modality. 4, 2

• Contrast-enhanced MRI can identify high-grade areas to guide biopsy site 1
• Most common in adults aged 30-60 years with better prognosis due to predominantly low-grade lesions 1, 5

Surgical Management

The goal is wide block resection with negative margins (R0), as narrower margins significantly increase local recurrence risk. 2

Key surgical principles: 2

• Limb-sparing surgery is now standard, with 90-95% of patients avoiding amputation
• Endoprosthetic or biological reconstruction following wide tumor resection is most common
• Surgical margins are crucial determinants of local control

Postoperative radiotherapy may be considered for radiosensitive tumors to reduce local recurrence risk. 2

Multidisciplinary Team Requirements

Management requires a multidisciplinary team with demonstrated expertise including: 1, 4

• Medical and radiation oncologists
• Orthopedic oncologists/surgeons
• Musculoskeletal radiologists and pathologists
• Nuclear medicine physicians
• Palliative care specialists

Follow-Up Protocol

Structured surveillance schedule for high-grade tumors: 4, 2

• Every 3 months for first 2 years
• Every 6 months for years 3-5
• Every 6-12 months for years 5-10
• Every 0.5-2 years thereafter

Each visit should include: 4, 2

• Local imaging of primary site
• Chest radiography or CT scan
• Pulmonary function evaluation when indicated
• Long-term surveillance for chemotherapy, surgery, and radiotherapy toxicities continuing beyond 10 years

Critical Pitfalls to Avoid

• Never perform biopsy before referral to specialized center - improper biopsy tract placement can compromise limb salvage 1
• Do not dismiss recent injury as explanation - trauma does not rule out malignancy and must not delay diagnostic workup 1
• Avoid weight-bearing on affected extremity during evaluation to prevent pathologic fracture 6
• Monitor for secondary cancers in survivors, which can occur related or unrelated to radiation therapy 4
• Long-term cardiac surveillance is essential as anthracycline-induced cardiac dysfunction can occur decades after treatment 4