What is the evidence for lattice radiotherapy (RT) in the treatment of soft tissue sarcoma?

Evidence for Lattice Radiotherapy in Soft Tissue Sarcoma

Current Evidence Base

Lattice radiotherapy (LRT) is an emerging technique for inoperable bulky soft tissue sarcomas with preliminary evidence showing feasibility and tolerability, but it is not yet established as standard therapy and lacks guideline endorsement. 1

The only available evidence comes from a single retrospective study of 15 patients with inoperable non-extremity sarcomas treated between 2020-2024, representing the most recent data on this technique. 1

Clinical Outcomes from Available Evidence

Treatment Response and Local Control

• 67% of patients achieved stable disease at 1-2 months follow-up based on RECIST 1.1 criteria after LRT combined with normo- or hypo-fractionated external beam radiotherapy. 1
• LRT enabled surgical resection in 5 of 15 patients (33%) who were initially deemed inoperable, with 3 of these patients alive without disease. 1
• All symptomatic patients reported symptom relief following LRT treatment. 1

Survival Outcomes

• Median follow-up was only 10 months (range 4-32 months), limiting long-term outcome assessment. 1
• Among non-operated patients (n=10), 50% died from disease progression while 50% remained alive, with three maintaining stable disease at 21-32 months. 1

Toxicity Profile

• Grade 2 toxicity occurred in 3 patients: gastrointestinal toxicity (2 patients) and asthenia (1 patient). 1
• Grade 3 toxicity occurred in 2 patients: esophagitis (1 patient) and inguinal dermatitis (1 patient). 1
• No Grade 4-5 acute or chronic toxicity was observed. 1

Technical Specifications from Available Data

The LRT technique utilized in the study involved:

• Median gross tumor volume of 1058 cm³ (range 142-6103 cm³), representing truly bulky disease. 1
• Median of 9 spheres (range 4-30) for spatial fractionation. 1
• Combination approach with conventional external beam radiotherapy. 1

Context Within Standard Sarcoma Radiotherapy Guidelines

Established Standard Approaches

Standard radiotherapy for soft tissue sarcomas involves:

• 50-60 Gy in 1.8-2 Gy fractions postoperatively, with boosts up to 66 Gy for positive margins, as recommended by ESMO. 2, 3
• Preoperative radiotherapy at 50 Gy for borderline resectable tumors to reduce treatment volumes and late toxicity. 3
• Definitive radiotherapy (66 Gy in 33 fractions) for unresectable tumors provides durable local control in selected patients. 3, 4

Comparison to Definitive RT Evidence

A larger retrospective study (n=116) of definitive modern radiotherapy for unresectable STS showed:

• 3-year local control of 43.2% and overall survival of 34% with median EQD2 of 60 Gy. 4
• EQD2 ≥64 Gy was associated with better overall survival. 4
• This represents substantially more robust evidence than the LRT data. 4

Critical Limitations and Caveats

Evidence Quality Issues

• Single-center retrospective study with only 15 patients represents the lowest tier of evidence. 1
• No comparison group or randomized design prevents assessment of whether LRT offers advantages over standard definitive radiotherapy. 1
• Short median follow-up of 10 months is insufficient to assess long-term local control or late toxicity. 1
• No guideline endorsement from NCCN, ESMO, or ASCO for LRT in soft tissue sarcomas. 2, 3

Patient Selection Bias

• All patients had "no treatment options or no response to systemic therapy," representing a highly selected, poor-prognosis population. 1
• The 33% conversion to resectability is notable but requires validation in larger cohorts. 1

Missing Critical Data

• No comparison to outcomes with standard definitive RT techniques (IMRT, VMAT, stereotactic RT) that are guideline-supported. 3, 4
• Unclear whether symptom relief was superior to palliative hypofractionated RT (30 Gy in 10 fractions), which has established efficacy. 3, 5

Clinical Recommendation

For inoperable bulky soft tissue sarcomas, standard definitive radiotherapy using modern techniques (IMRT, VMAT) at doses of 60-66 Gy remains the evidence-based approach. 3, 4

LRT may be considered only in highly selected cases within clinical trial settings or when standard definitive RT has failed or is not feasible, given the preliminary nature of evidence limited to 15 patients with short follow-up. 1

For patients requiring rapid palliation, established hypofractionated regimens (30 Gy in 10 fractions or 40 Gy in 15 fractions) have proven safety and efficacy. 3, 5

The decision to use LRT should occur only after multidisciplinary tumor board discussion at a high-volume sarcoma center, with clear documentation that standard approaches have been exhausted or are contraindicated. 3