What is the role of radiotherapy (radiation therapy) in soft tissue sarcomas?

Role of Radiotherapy in Soft Tissue Sarcomas

Radiotherapy combined with surgery is the standard local treatment for most soft tissue sarcomas, improving local control rates significantly compared to surgery alone, though it does not improve overall survival. 1, 2

Primary Indications for Radiotherapy

Radiotherapy is routinely recommended for the following presentations:

• High-grade, deep tumors >5 cm - This is the clearest indication, with radiotherapy improving local control from approximately 70-80% to 91-100% 1
• High-grade, deep tumors <5 cm - Also treated with surgery plus radiotherapy, though some centers debate this in multidisciplinary settings 1
• Positive or close surgical margins (R1/R2 resections) - When re-excision cannot achieve adequate margins without major morbidity 1

Radiotherapy is selectively recommended for:

• Low-grade, superficial tumors >5 cm 1
• Low-grade, deep tumors <5 cm 1
• Low-grade tumors >5 cm - Decision based on anatomical site and expected sequelae versus histological aggressiveness 1

Radiotherapy is generally not needed for:

• Small (<5 cm), widely excised tumors with negative margins 3
• Truly compartmental resections with tumor entirely contained within the compartment 1

Preoperative vs Postoperative Timing

The choice between preoperative and postoperative radiotherapy depends on specific clinical factors 1, 2:

Preoperative radiotherapy (50-50.4 Gy in 1.8-2 Gy fractions) is preferred when:

• Smaller treatment volumes are desired to reduce late toxicity 1, 2
• Tumor is borderline resectable and downsizing would facilitate surgery 1
• Radiosensitive histology (e.g., myxoid liposarcoma) where significant shrinkage is expected 1
• Patient has anatomic constraints where minimizing radiation field is critical 1

Postoperative radiotherapy (60-66 Gy in 1.8-2 Gy fractions) is preferred when:

• Tumor is rapidly growing or painful, requiring urgent surgery 1
• Wound healing complications are anticipated based on location or patient factors 1
• Definitive pathology is needed to guide treatment decisions 2

Key trade-off: Preoperative radiotherapy causes higher rates of acute wound complications (35% vs 17%), while postoperative radiotherapy causes more late fibrosis and functional impairment 1, 2. Recent evidence shows short-course hypofractionated preoperative schedules (25-30 Gy in 5 fractions) achieve equivalent local control without increased toxicity 1.

Dosing Schedules

Standard postoperative dosing: 50-60 Gy in 1.8-2 Gy fractions, with boosts up to 66 Gy depending on margin status 1, 4

For positive microscopic margins: Add 16-18 Gy boost (total ~66-68 Gy) 1, 4

For gross residual disease: Add 20-26 Gy boost (total ~70-76 Gy) if normal tissue can be spared 1, 4

Standard preoperative dosing: 50 Gy in 25-28 fractions 1

Dose-painted preoperative approach: 45-50 Gy to entire tumor with simultaneous integrated boost to 57.5 Gy to high-risk margins, with no additional boost after surgery 1

Important caveat: Postoperative boost after preoperative radiotherapy does not improve local control rates and may increase late toxicity, so it should not be routinely used even with positive margins 1, 5

Special Situations

Retroperitoneal sarcomas: The role of radiotherapy is controversial. The STRASS trial showed no abdominal recurrence-free survival benefit with preoperative radiotherapy, though subgroup analyses suggested potential benefit for liposarcoma and low-grade tumors 6. Preoperative radiotherapy (45-50 Gy) may be considered selectively for high-risk patients, with dose-painted boost to 57.5 Gy to posterior margins at highest risk 1, 6

Unresectable or marginally resectable tumors: Definitive radiotherapy alone can provide durable local control, with doses of 66 Gy in 33 fractions recommended 1. Outcomes correlate with tumor size, grade, and radiation dose 1

Regional lymph node metastases: Combine wide excision with adjuvant radiotherapy and chemotherapy for sensitive histotypes, as this represents likely systemic disease 1

Palliative settings: Multiple fractionation schemes available (8 Gy single fraction, 20 Gy in 5 fractions, 30 Gy in 10 fractions, etc.) based on clinical scenario 1

Alternative Radiation Techniques

Intraoperative radiotherapy (IORT): 10-12.5 Gy for microscopically positive margins, 15 Gy for gross disease 1. One small trial showed improved local control (60% vs 20%) compared to postoperative external beam alone in retroperitoneal sarcomas 1

Brachytherapy: Option in selected cases, particularly for high-grade extremity sarcomas where it improved local control (91% vs 70%) in one randomized trial 1

Proton beam therapy: Considered for spinal/paraspinal locations and in children/young adults to minimize late toxicity 1

Intensity-modulated radiotherapy (IMRT): Preferred modern technique allowing better tumor coverage while sparing normal tissues 1, 2

Critical Pitfalls to Avoid

• Do not omit radiotherapy for high-grade, deep tumors >5 cm even with negative margins - local recurrence rates drop from 20-30% to <10% with radiotherapy 1
• Do not add postoperative boost after preoperative radiotherapy for positive margins - this increases toxicity without improving control 1, 5
• Do not delay surgery more than 8 weeks after preoperative radiotherapy 1
• Include the postoperative hematoma in the treatment volume as it represents potential tumor contamination 4
• Consider radiotherapy even for low-grade tumors if >5 cm or marginally excised, as local recurrence and late metastases can occur up to 10 years later 3