Is lattice radiotherapy a viable treatment option?

Lattice Radiotherapy: An Emerging Treatment for Large, Bulky Tumors

Lattice radiotherapy (LRT) is a viable and innovative treatment option specifically designed for large tumors (>5 cm) that are not amenable to conventional stereotactic body radiotherapy (SBRT), with early clinical evidence demonstrating safety and promising tumor response rates. 1, 2

What is Lattice Radiotherapy?

Lattice radiotherapy represents a modern form of spatially fractionated radiation therapy (SFRT) that delivers ablative doses to large tumors through a unique geometric pattern 1, 3:

• Delivers 20 Gy in 5 fractions to the entire tumor volume with simultaneous integrated boost to 66.7 Gy arranged in a defined geometric lattice pattern 1
• Administered every other day to allow for biological recovery between fractions 1
• Uses volumetric modulated arc therapy (VMAT) technology available on standard linear accelerators 3

The technique creates high-dose "vertices" or spheres within the tumor while maintaining lower doses to the surrounding tissue, theoretically triggering an immune-mediated bystander effect that extends tumor control beyond the directly irradiated volumes 4.

Clinical Evidence for Safety

Phase I Trial Results

The LITE SABR M1 phase I trial (2019-2020) established the safety profile of lattice SBRT 1:

• Enrolled 20 patients with 22 tumors, median volume 579.2 cc (range: 54.2-3713.5 cc) 1
• Median tumor diameter 11.1 cm (range: 5.6-21.4 cm) 1
• Zero cases of likely treatment-associated grade 3+ toxicity in the 90-day acute period 1
• One case of grade 4 toxicity possibly (but not definitely) associated with treatment 1

Systematic Review Findings

A 2023 systematic review of 81 patients (84 lesions) treated with LRT across multiple institutions confirmed the safety signal 2:

• Excluding two severe toxicities with questionable relation to LRT, available clinical experience confirms LRT safety 2
• Tumor volumes ranged from 63.2 cc to 3713.5 cc 2
• Various anatomical sites treated: 50% thorax, 45% abdomen/pelvis, 5% extremity 1

Clinical Evidence for Efficacy

Tumor Response Rates

While complete response is not always achieved, LRT demonstrates meaningful tumor reduction 2:

• When complete response not achieved at 3-6 months post-LRT, median lesion reduction approximately ≥50% was registered 2
• Dramatic tumor responses reported with minimal side effects in multiple case series 3

MRI-Based Lattice Experience

A gynecological case report demonstrated impressive results with MRI-guided lattice radiotherapy 5:

• Patient with large pelvic recurrence of uterine serous papillary carcinoma achieved almost complete clinical response 5
• Long-lasting symptom relief maintained 5
• Patient alive 20 months post-treatment with no radiation-related toxicities 5

Technical Implementation

Planning Parameters

The standard lattice SBRT approach follows these specifications 1, 4:

• Prescription: 20 Gy in 5 fractions to planning target volume (PTV) 1
• Simultaneous integrated boost: 66.7 Gy to lattice vertices 1
• Vertex spacing: typically 3-5 cm apart in geometric arrangement 4
• All plans must meet AAPM Task Group 101 dose constraints 3

Quality Assurance

Feasibility studies confirm deliverability on standard equipment 3:

• Plans generated using commercially available treatment planning systems 3
• Delivered on clinically available linear accelerators 3
• Quality assurance includes portal imaging and ion chamber verification 3

Clinical Indications

Appropriate Patient Selection

Lattice radiotherapy should be considered for 1, 2, 3:

• Tumors >5 cm in greatest axial dimension 1
• Metastatic and/or unresectable tumors where conventional SBRT is limited by size 1, 3
• Bulky tumors requiring palliation where standard radiotherapy doses would exceed organ-at-risk tolerance 3
• Deep-seated tumors ≥10 cm where technical delivery of conventional SBRT is challenging 3

Anatomical Sites

Clinical experience encompasses 1, 5:

• Thoracic tumors (50% of treated cases) 1
• Abdominal/pelvic tumors (45% of treated cases) 1
• Extremity tumors (5% of treated cases) 1
• Gynecological malignancies (case reports) 5

Important Caveats and Limitations

Evidence Quality

The current evidence base is limited to early-phase trials and case series, precluding definitive conclusions about long-term efficacy 2:

• Very low level of evidence overall 2
• Significant heterogeneity across studies in terms of tumor types, volumes, and treatment parameters 2
• No randomized controlled trials comparing LRT to standard approaches 2

Current Practice Status

LRT remains largely based on heuristic principles rather than robust biological optimization 4:

• Over 150 patients worldwide have received LRT since 2014 4
• Ongoing phase II clinical trial (NCT04553471, NCT04133415) evaluating late safety and efficacy 1, 3
• Should be considered investigational and ideally delivered within clinical trial protocols 1

Technical Considerations

Successful implementation requires specific expertise and equipment 3, 4:

• Requires volumetric modulated arc therapy capability 3
• Demands rigorous quality assurance protocols 3
• Planning complexity exceeds standard SBRT 4

Comparison to Standard Radiotherapy

Unlike conventional radiotherapy approaches for large tumors 6:

• Standard SBRT is typically limited to smaller lesions due to toxicity concerns 1, 3
• Conventional fractionated radiotherapy for bulky tumors delivers lower, palliative doses 5
• Lattice allows ablative dosing to large volumes while maintaining acceptable toxicity profiles 1, 3