Bone Cancer

Chondrosarcoma

Background:

• Most common bone cancer in adults (40%)

• Most frequent sites of origin: Pelvis and proximal femur

• Characterized by malignant cartilage matrix production without osteoid

• Bony destruction + calcification

• Very chemoresistant

• Subtypes:

  • Conventional (90%)

  • Non-conventional (10%)

    • Clear cell

    • Dedifferentiated

    • Mesenchymal

    • Myxoid

    • Juxtacortical

Treatment:

• If resectable: Surgery 

• If metastatic/not resectable: systemic therapy

  • Ivosidenib (If IDH1 mutation)

  • Pazopanib

  • Dasatinib

  • Pembrolizumab (if TMB >10 or MSI-H)

• If recurrence: reexcision

• If mesenchymal chondrosarcoma: Treat like ewing sarcoma

• If dedifferentiated chondrosarcoma: Treat like osteosarcoma

Surveillance:

• Long-term due to risk of late recurrence and metastasis

• Chest imaging for at least 10 years

Osteosarcoma

Background:

• Bimodal distribution:

  • 10-20 and 60-80 years old

• Presents as hard mass and bone pain

• Prognostic factors:

  • Tumor site (axial location is associated with worse prognosis compared to extremity)

  • Tumor size

  • Age (older age is associated with worse prognosis)

  • Presence and number of metastases at diagnosis

  • Histologic response to neoadjuvant chemotherapy

    • ≥90% tumor necrosis after treatment is a good response and strongly predicts improved survival

  • Negative/positive margin of surgical resection

Diagnosis:

• Lytic/blastic features on X-Ray “Sunbursting” (Buzz word)

• Require core needle biopsy/excisional biopsy

Treatment:

• Low grade:

  • Surgery if localized

• High grade:

  • Always chemo x3 cycles → surgery → chemo x3 cycles

    • Regardless of how much necrosis was present on surgical pathology

    • Regimen:

      • MAP: Methotrexate+ Doxorubicin (Adriamycin) + Cisplatin

        • Especially preferred for patients <40 years with excellent ECOG

      • AP: if patient cannot tolerate high dose Methotrexate

• Metastatic:

  • If oligometastatic

    • Surgery particularly for lung mets: Potentially curative

  • Medications:

    • AP (if not already given) 

    • Ifosphamide 

    • Gemcitabine

    • Regorafenib

    • Cabozantinib

Ewing Sarcoma

Background:

• Presents with “onion skinning” pattern on xray (Buzz word)

• PET/CT scan for staging

• Consider BMBx to see if bone marrow involvement

Treatment:

• Chemo regimens:

  • VDC/IE:

    • Vincristine, Doxorubicin, Cyclophosphamide alternating with Ifosfamide and Etoposide

  • VIDE:

    • Vincristine, Ifosfamide, Doxorubicin, Etoposide

  • VAIA:

    • Vincristine, Dactinomycin (Actinomycin D), Ifosfamide, Doxorubicin (Actinomycin)

• Localized disease:

  • Chemo → restaging →

    • If stable/improved: → RT or Surgery

    • If progressive: → RT ± surgery → Chemo

• Metastatic Disease:

  • Oligometastatic: Surgery or chemoRT (same as localized disease)

  • Widely metastatic: Chemo

    • First line:

      • VDC/IE (best response)

      • VIDE

      • VAIA

    • Second line:

      • Temodar + Irinotecan

      • Topotecan + cyclophosphamide

      • Cabozantinib

      • High dose ifosfamide

  
  

Chordoma

Background:

• Arising from notochordal remnants

• Mostly in age 40–75

• Typically located in the sacrum, skull base and spine

• Slow-growing but locally aggressive

Treatment:

• Surgery (resection with wide margins) and adjuvant high-dose RT

• Generally chemoresistant

• Adjuvant high-dose radiation is recommended for positive margins or unresectable disease

• If recurrent: Surgery ± RT ± systemic therapy (same as medications for chondrosarcoma)

  • Pazopanib

  • Dasatinib

  • Pembrolizumab (if TMB >10 or MSI-H)

Giant Cell Tumor of Bone (GCTB)

Background:

• rare (5%), mostly affecting adults aged 20–40 years

• Locally aggressive with high rate of local recurrence

• Rarely metastasize to the lungs or undergo malignant transformation to high-grade sarcoma, especially after radiation therapy

• Typically arising in the meta-epiphyseal regions of long bones (distal femur and proximal tibia)

• Neoplastic stromal cells and numerous osteoclast-like giant cells, driven by RANKL overexpression, which leads to bone resorption and local destruction.

Treatment:

• If resectable: Surgery

  • Preferably intralesional curettage with local adjuvants (phenol, liquid nitrogen, cement)

• If unresectable: Denosumab (RANKL inhibitor)