Chemotherapy For Bone Tumors

Indications

• Osteosarcoma: Neoadjuvant and adjuvant chemotherapy are standard components of treatment.

• Ewing Sarcoma: Highly chemosensitive; systemic therapy is essential for all patients.

• Chondrosarcoma: Generally resistant to conventional chemotherapy; only the dedifferentiated and mesenchymal subtypes may respond.

• Other rare tumors (e.g., MFH/UPS, Angiosarcoma): Chemotherapy considered in high-grade or metastatic cases.

Chemotherapy Timing

Type Purpose Typical Use     Neoadjuvant Shrink tumor, facilitate limb-salvage surgery, evaluate histologic response Osteosarcoma, Ewing Sarcoma   Adjuvant Eliminate residual micrometastatic disease Osteosarcoma   Palliative Control symptoms or progression in unresectable/metastatic disease All high-grade sarcomas

Evaluation of Response

• Histologic response is assessed by percentage of tumor necrosis in resected specimens:
  90% necrosis → good responder<90% necrosis → poor responder

• Imaging: MRI and PET-CT can aid in preoperative assessment but are less reliable than pathology.

• Prognostic impact: Histologic response remains one of the strongest predictors of overall survival.

Toxicities and Supportive Care

• Acute toxicities: Myelosuppression, mucositis, nausea/vomiting, nephrotoxicity (cisplatin), and cardiotoxicity (doxorubicin).

• Long-term complications: Ototoxicity, infertility, secondary malignancies, and renal or cardiac dysfunction.

• Supportive strategies:Adequate hydration and mesna for ifosfamide/cyclophosphamide
  Dexrazoxane for anthracycline cardioprotection
  Growth factor support (G-CSF) to reduce neutropenia
  

Emerging Therapies

• Targeted therapy: IGF-1R inhibitors, mTOR inhibitors, and VEGF-targeted agents show limited but growing promise.

• Immunotherapy: Research into checkpoint inhibitors and cell-based therapies (e.g., CAR-T) is ongoing, particularly in relapsed Ewing sarcoma.

• Chemo-sensitivity modulation: Nanocarrier drug delivery and combination regimens are under investigation to improve efficacy while minimizing toxicity.

Key Points

• Chemotherapy is mandatory for osteosarcoma and Ewing sarcoma, but ineffective for most low-grade chondrosarcomas.

• Histologic necrosis after neoadjuvant therapy remains a critical prognostic factor.

• Ongoing trials aim to optimize drug combinations and identify predictive biomarkers for response.

References

1. Bielack SS et al. Osteosarcoma: ESMO Clinical Practice Guidelines. Ann Oncol. 2022;33(12):1344–1356.

2. Ladenstein R et al. Ewing Sarcoma: Current Management and Future Directions. J Clin Oncol. 2021;39(26):3039–3053.

3. Palmerini E et al. Chemotherapy in Chondrosarcoma: When and Why? Eur J Cancer. 2020;140:74–83.

4. Ferrari S et al. MAP and Beyond: New Horizons in Osteosarcoma Chemotherapy. Cancer Treat Rev. 2023;114:102516.