Are sarcomas sensitive to chemotherapy and radiation therapy?

Chemotherapy and Radiation Sensitivity of Sarcomas

Sarcomas demonstrate variable sensitivity to chemotherapy and radiation therapy, with significant differences based on histological subtypes, making individualized treatment essential for optimal outcomes.

Chemotherapy Sensitivity

• Response rates to chemotherapy in soft tissue sarcomas (STS) vary considerably, ranging from 10% to 50% depending on the drugs used, patient selection, and histological subtype 1.

• Certain histological subtypes show higher sensitivity to chemotherapy:

  • Synovial sarcoma, leiomyosarcoma, and myxoid liposarcoma have demonstrated higher response rates to chemotherapy 1.
  • Ewing sarcoma is generally considered chemotherapy-sensitive, with standard regimens including doxorubicin and ifosfamide 1.

• Other subtypes are notably resistant to conventional chemotherapy:

  • Alveolar soft part sarcoma, extraskeletal myxoid chondrosarcoma, and solitary fibrous tumors are generally regarded as insensitive to chemotherapy 1.
  • Clear cell sarcoma has only occasional reports of responses to chemotherapy 1.
  • Most chondrosarcomas (except mesenchymal subtype) are resistant to conventional chemotherapy 1.

• Patient factors associated with better chemotherapy response include:

  • Good performance status
  • Younger age
  • Absence of liver metastases 1

Radiation Sensitivity

• Radiation therapy is a standard component of treatment for many soft tissue sarcomas, particularly for deep tumors with a diameter >5 cm 1.

• Radiation sensitivity also varies by histological subtype:

  • Solitary fibrous tumors show notable sensitivity to radiation therapy 1.
  • Chondrosarcomas are generally considered resistant to conventional radiotherapy, with the exception of skull base chondrosarcomas which respond well to high-dose radiation therapy, including proton beam or carbon ion radiotherapy (80-90% local control rates) 1.
  • Mesenchymal chondrosarcoma may be more sensitive to both chemotherapy and radiation 1.

• For Ewing sarcoma, radiation therapy is commonly used as part of multimodal treatment, though one study suggested that in adult extraskeletal Ewing sarcoma patients treated with chemotherapy and surgery, the addition of radiation therapy did not improve overall survival 2.

Histology-Specific Considerations

• Mesenchymal chondrosarcoma is more chemotherapy-sensitive than other chondrosarcoma subtypes and may benefit from adjuvant or neoadjuvant therapy with Ewing-type chemotherapy regimens 1.
• Dedifferentiated chondrosarcoma is often treated as a high-grade bone sarcoma with chemotherapy, though its sensitivity remains uncertain 1.
• For retroperitoneal sarcomas (RPS), a systematic review found no evidence that adding chemotherapy to surgery improves recurrence-free survival or overall survival 1.

Treatment Approaches Based on Sensitivity Patterns

• For chemotherapy-sensitive histologies, multiagent chemotherapy with anthracyclines plus ifosfamide may be preferred, especially when tumor response is important 1.

• For chemotherapy-resistant subtypes, targeted therapies are emerging as alternatives:

  • Extraskeletal myxoid chondrosarcoma: Pazopanib or sunitinib 1
  • Solitary fibrous tumor: Anti-angiogenic tyrosine kinase inhibitors 1
  • Alveolar soft part sarcoma: Anti-angiogenic tyrosine kinase inhibitors or checkpoint inhibitors 1

• Radiation therapy should be considered as standard treatment for deep soft tissue sarcomas >5 cm, typically administered postoperatively at doses of 50-60 Gy 1.

• Chemosensitivity testing is feasible in soft tissue sarcomas and can help create sensitivity profiles for cytotoxic agents, though this approach is not yet standard practice 3.

Emerging Approaches

• Radiosensitizing agents may improve cancer control when combined with radiation therapy:

  • Ifosfamide and newer activated ifosfamide agents have potential to improve sarcoma control when combined with radiation 4.
  • Other outpatient radiosensitization regimens include gemcitabine, temozolomide, or combinations of temozolomide and irinotecan 4.

• For Ewing sarcoma, targeted therapies under investigation include IGF1R inhibitors, mTOR inhibitors, PARP inhibitors, and tyrosine kinase inhibitors, though with limited efficacy as single agents 5.

• Treatment decisions should be made by multidisciplinary teams at specialized sarcoma centers, with consideration of clinical trials when appropriate 1.