What types of soft tissue sarcoma in adults are responsive to radiotherapy?

Radiotherapy-Responsive Soft Tissue Sarcomas

Most adult soft tissue sarcomas benefit from radiotherapy when combined with surgery, particularly high-grade, deep tumors >5 cm, but myxoid liposarcoma demonstrates exceptional radiosensitivity with superior local control rates compared to all other subtypes.

Sarcomas with Standard Radiotherapy Indications

High-Risk Features Requiring Radiotherapy

Radiotherapy is standard treatment for intermediate-to-high grade, deep soft tissue sarcomas >5 cm in diameter when combined with surgical resection. 1 This applies broadly across most histologic subtypes and improves local control, though not overall survival. 1

Key indications include:

• High-grade tumors (G2-3), deep location, >5 cm diameter - this represents the strongest indication for adjuvant radiotherapy 1, 2
• Deep lesions ≤5 cm - radiotherapy is an option in selected cases 1
• Large or marginally excised low-grade tumors - selected patients benefit from radiotherapy 1
• R1 (microscopically positive) or R2 (grossly positive) margins that cannot be re-excised 1, 2

Specific Histologic Subtypes with Enhanced Radiosensitivity

Myxoid liposarcoma demonstrates exceptional radiosensitivity compared to other soft tissue sarcomas. 3 This translates into:

• 97.7% five-year local recurrence-free survival with combined surgery and radiotherapy, compared to 89.6% for other sarcoma subtypes 3
• Dose reduction is safe and effective - the DOREMY trial demonstrated that 36 Gy in 2-Gy fractions (rather than standard 50 Gy) achieved 91% extensive pathologic response with 100% local control and only 17% wound complication rate 4
• Superior systemic disease control with 93.9% five-year overall survival versus 76.4% for other sarcomas 3

Chemotherapy-sensitive subtypes that may warrant consideration of radiotherapy include:

• Synovial sarcoma 1, 2
• Myxoid round cell sarcoma 1
• Uterine leiomyosarcoma 1
• Desmoplastic small round cell tumor 1

Radiotherapy Dosing and Sequencing

Preoperative Radiotherapy (Preferred)

Preoperative radiotherapy is strongly recommended over postoperative radiotherapy when radiotherapy is indicated. 5 Standard dose is 50 Gy in 25 fractions delivered over 5 weeks. 1

Advantages include:

• Lower total radiation dose required 5
• Smaller treatment volumes 5
• Potential tumor shrinkage facilitating surgery 1

Exception: Myxoid liposarcoma can be treated with reduced dose of 36 Gy in 18 fractions preoperatively. 4

Postoperative Radiotherapy

Postoperative radiotherapy dose is 50-60 Gy in 1.8-2 Gy fractions, with boosts up to 66 Gy depending on margin status and presentation. 1, 2

For positive margins:

• R1 resections: add 16-18 Gy boost 2
• R2 resections: add 20-26 Gy boost 2

Alternative hypofractionated regimen of 50 Gy in 20 fractions (2.5 Gy per fraction) is acceptable for extremity sarcomas, particularly in older adults. 2

Definitive Radiotherapy for Unresectable Disease

For unresectable tumors or those requiring mutilating surgery, definitive radiotherapy alone can provide durable local control in selected cases. 1

• Recommended dose: 66 Gy in 33 fractions over 6.5 weeks for definitive treatment 1
• Outcomes correlate with tumor size, grade, and radiation dose 1
• All patients with unresectable disease died in one pediatric series, suggesting poor outcomes even with high-dose radiotherapy, justifying treatment intensification efforts 6

Alternative approaches for unresectable disease:

• Regional hyperthermia combined with chemotherapy - improves local progression-free survival and disease-free survival in high-grade, deep-seated tumors >5 cm 7
• Isolated hyperthermic limb perfusion with TNFα + melphalan for extremity-confined tumors 1, 7

Advanced Radiotherapy Techniques

Intensity-modulated radiation therapy (IMRT) and proton beam therapy enhance dose conformation and reduce normal tissue toxicity. 8

Proton therapy is indicated for:

• Spinal and paraspinal bone and soft tissue sarcomas in adults 1
• Broader indications in children and teenagers to reduce late toxicity 1
• Skull base sarcomas 8

Brachytherapy and intraoperative radiation therapy (IORT) are options in selected cases for microscopic residual disease. 1, 8

Critical Caveats

• Compartmental resection of intracompartmental tumors does not require adjuvant radiotherapy 1
• Preoperative radiotherapy increases acute wound healing complications but reduces late toxicity compared to postoperative treatment 1, 5
• Radiotherapy improves local control but not overall survival in soft tissue sarcomas 1, 2
• Retroperitoneal sarcomas: routine postoperative RT is not recommended; preoperative RT is preferred if radiotherapy is used 5