What is lattice radiotherapy?

What is Lattice Radiotherapy?

Lattice radiotherapy (LRT) is a modern form of spatially fractionated radiation therapy that delivers high-dose radiation to discrete spherical vertices (hot spots) arranged in a geometric pattern within large tumors, while the remainder of the tumor receives lower doses (cold spots), enabling safe treatment of bulky tumors (typically >5 cm) that would otherwise exceed normal tissue tolerance with conventional homogeneous radiation. 1, 2

Technical Characteristics and Delivery

Lattice SBRT delivers a heterogeneous dose distribution with vertices receiving 66.7 Gy in 5 fractions while the surrounding tumor receives 20 Gy in 5 fractions, delivered every other day. 1 The key dosimetric feature is the valley-to-peak dose ratio, which quantifies the degree of spatial fractionation between the lower-dose regions (valleys/cold spots) and higher-dose regions (peaks/vertices/hot spots). 3

Vertex Configuration

• Vertices are modeled as spheres with diameters of 1 cm, 1.5 cm, or 2 cm, arranged in square lattices with center-to-center distances of 2-5 cm, alternating along the superior-inferior direction. 4
• The optimal lattice configurations are those with center-to-center distances of 2.5-3.5 cm for 1.5 cm diameter vertices and 4 cm for 1 cm diameter vertices, characterized by high dose heterogeneity (median GTV D90%/D10% between 0.06 and 0.19). 4
• The prescription dose is typically that 50% of each vertex volume receives at least 20 Gy in one fraction. 4

Technical Delivery

• Lattice SBRT is delivered using volumetric modulated arc therapy (VMAT) on standard linear accelerators, with automated treatment planning now available through Eclipse Scripting API. 2, 4
• All generated plans meet standard SBRT dose constraints from AAPM Task Group 101, with quality assurance performed using external portal imaging device and ion chamber analyses. 2
• MRI-based Lattice radiotherapy using Apparent Diffusion Coefficient maps can guide boost placement followed by normofractionated radiotherapy. 5

Clinical Indications and Patient Selection

Lattice radiotherapy is specifically indicated for patients with large tumors (>5 cm, often >10 cm in axial dimension) who have metastatic and/or unresectable cancer requiring palliation or cytoreduction, where conventional SBRT would exceed normal tissue tolerance. 1, 2

Tumor Characteristics

• Median treated tumor volumes range from 150-1350 cm³ (median 494 cm³), with greatest axial diameters of 5.6-21.4 cm (median 11.1 cm). 1, 4
• Common anatomic sites include thorax (50%), abdomen/pelvis (45%), and extremity (5%). 1
• Bulky gynecological tumors, including locally advanced uterine serous papillary carcinoma with pelvic recurrence, are amenable to MRI-based Lattice approaches. 5

Radiobiological Mechanisms

The therapeutic effect of Lattice radiotherapy relies on three key mechanisms: radiation-induced bystander effects in low-dose regions, vascular alterations throughout the tumor, and immunologic interactions triggered by the heterogeneous dose distribution. 3

• High-dose vertices deliver ablative radiation to discrete tumor subvolumes while restricting the remainder to safer lower doses, limiting toxicity to adjacent normal tissues. 2, 3
• The valley-to-peak ratio quantifies spatial fractionation and enables delivery of high doses without exceeding tolerance of adjacent critical structures. 3

Clinical Outcomes and Safety

A prospective phase I trial (LITE SABR M1) demonstrated no likely treatment-associated grade 3+ toxicity in the 90-day period, with only one case of grade 4 toxicity possibly associated with Lattice SBRT, meeting its primary endpoint of short-term safety. 1

Efficacy Data

• Clinical experience shows almost complete response with long-lasting symptom relief in bulky gynecological tumors, with patients remaining alive 20 months post-treatment without radiation-related toxicities. 5
• Dramatic tumor response and minimal side effects have been reported with spatially fractionated radiation therapy approaches for large tumors. 2

Treatment Planning Efficiency

• Automated Lattice planning requires median times of 1 minute for segmentation and 21 minutes for dose optimization and calculation. 4
• The number of vertices strongly correlates with GTV volume (r > 0.85, p < 0.001) across all lattice configurations. 4

Critical Implementation Considerations

Lattice radiotherapy requires volumetric modulated arc therapy capability, automated treatment planning software, and rigorous quality assurance protocols including external portal imaging and ion chamber verification. 2, 4

Common Pitfalls to Avoid

• Do not attempt Lattice SBRT without meeting standard SBRT dose constraints (AAPM TG-101) for organs at risk, as the technique's safety depends on restricting dose to critical structures despite treating large volumes. 2
• Avoid using Lattice radiotherapy for tumors <5 cm where conventional SBRT can safely deliver homogeneous ablative doses. 1
• Do not deliver Lattice SBRT on consecutive days; treatment should be given every other day to allow for normal tissue recovery. 1

Ongoing Clinical Development

Lattice SBRT is currently being evaluated in ongoing phase II clinical trials (NCT04553471, NCT04133415) to assess late safety and efficacy for patients with metastatic cancer requiring palliation of large tumors. 2