What is the standard neoadjuvant external-beam radiotherapy dose and fractionation for a typical adult with a resectable soft‑tissue sarcoma of the extremity or trunk wall?

Standard Neoadjuvant Radiotherapy Dose for Soft Tissue Sarcoma

The standard neoadjuvant (preoperative) external-beam radiotherapy dose for resectable soft tissue sarcoma of the extremity or trunk wall is 50 Gy delivered in 25 fractions of 1.8-2 Gy over 5 weeks. 1

Dose and Fractionation Specifications

Conventional Fractionation (Standard of Care)

• Total dose: 50 Gy delivered in 25-28 fractions 1
• Fraction size: 1.8-2 Gy per fraction 1, 2
• Treatment duration: 5-6 weeks 1, 2
• This regimen is endorsed by both NCCN and ESMO-EURACAN-GENTURIS guidelines as the standard approach 1

Emerging Hypofractionated Regimens

• Alternative short-course option: 25-30 Gy in 5 fractions (5-6 Gy per fraction) delivered over 1 week has shown comparable local control rates without increased toxicity in recent studies 3, 4
• The hypofractionated approach may be particularly effective for radiosensitive histologies such as myxoid liposarcoma 3
• Surgery should occur 4-8 weeks after completion of radiotherapy regardless of fractionation schedule 1, 3

Post-Surgical Boost Considerations

If margins are positive after preoperative radiotherapy and surgical resection, additional radiation may be required 1:

• Microscopically positive margins (R1): 16-18 Gy boost 1
• Gross residual disease (R2): 20-26 Gy boost 1
• However, if wide margins are obtained after preoperative RT, no additional radiation is needed 1

Comparison to Postoperative Radiotherapy

The preoperative approach uses a lower total dose (50 Gy) compared to postoperative radiotherapy (60-66 Gy) because the tumor is well-oxygenated and the treatment volume is smaller 1, 5. The landmark randomized trial by O'Sullivan et al. demonstrated that preoperative 50 Gy in 25 fractions achieved equivalent local control to postoperative 66 Gy in 33 fractions 5.

Critical Advantages of Preoperative Radiotherapy

• Smaller treatment volumes since the operative field does not need to be covered 1, 6
• Better offset of R1 margin impact compared to postoperative RT 1
• Reduced long-term morbidity including less fibrosis, edema, bone fracture, and joint stiffness 1
• Facilitates limb-sparing surgery when preservation of critical structures is the goal 1

Important Caveats

Wound Complications

• Preoperative RT increases acute wound healing complications to 35% compared to 17% with postoperative RT 5
• This risk is particularly elevated with primary closure techniques 1
• Consider plastic surgery involvement to minimize wound complications 1
• Modern IMRT techniques may reduce this historically reported complication rate 1

Timing Considerations

• Allow 3-6 weeks interval between RT completion and surgery to permit acute radiation reactions to subside 1
• Avoid very long intervals before surgery to prevent late fibrosis development 1

When Radiotherapy May Be Omitted

• Truly compartmental resections with tumor entirely contained within the compartment do not require RT 1
• Low-grade tumors are mostly treated with surgery alone, though RT can be considered on an individualized basis 1
• Decision should account for tumor size, histological type, expected margins, and consequences of local recurrence 1

Technical Delivery

• Use advanced techniques (IMRT, image-guided RT, or particle therapy) when available to improve dose conformation and reduce normal tissue toxicity 1, 6
• Total doses must always be determined by normal tissue tolerance 1