The Technical and Clinical Implementation of LATTICE Radiation Therapy (LRT)

Abstract

The concept of spatially fractionated radiation therapy (SFRT) was conceived over 100 years ago, first in the form of GRID, which has been applied to clinical practice since its early inception and continued to the present even with markedly improved instrumentation in radiation therapy. LATTICE radiation therapy (LRT) was introduced in 2010 as a conceptual 3D extension of GRID therapy with several uniquely different features. Since 2014, when the first patient was treated, over 150 patients with bulky tumors worldwide have received LRT. Through a brief review of the basic principles and the analysis of the collective clinical experience, a set of technical recommendations and guidelines are proposed for the clinical implementation of LRT. It is to be recognized that the current clinical practice of SFRT (GRID or LRT) is still largely based on the heuristic principles. With advancements in basic biological research and the anticipated clinical trials to systemically assess the efficacy and risk, progressively robust optimizations of the technical parameters are essential for the broader application of SFRT in clinical practice.

Combined High-Dose LATTICE Radiation Therapy and Immune Checkpoint Blockade for Advanced Bulky Tumors: The Concept and a Case Report

“…This is consistent with a number of research works favoring high dose for effective anti-tumor T-cell priming (20,21,25,30), and that when combined with low-dose treatment, radiation-induced immune modulation might be augmented (38,39). Additionally, it has been postulated that the low dose regions (valleys) might preserve the perfusion needed for circulating the factors essential for anti-tumor immunity (10,(40)(41)(42)(43)(44).…”

“…The first patient with locally advanced lung cancer treated with LRT followed by conventionally fractionated radiotherapy, combined with chemotherapy demonstrated excellent clinical response after 6 years follow-up (13). Since 2010, over 150 patients have been treated with LRT and more reports of clincal outcomes are anticipated (10). However, to this day, LRT alone as induction of anti-tumor T-cell immunity, to combine with immune checkpoint blockade treatment has not been reported.…”

“…Spatially fractionated radiotherapy (SFRT) with GRID, proposed in 1909 and further developed since early 1950s, has been safely utilized for the treatment of bulky and advanced tumors with impressively accumulated clinical data (6)(7)(8). In recent years, the 2D GRID technique was extended to a 3D configuration, known as LATTICE radiotherapy (LRT) (9,10). The safety and clinical efficacy of LRT has been reported in various voluminous tumors (11)(12)(13)(14)(15).…”

“…Based on the results of radiobiological studies, the possible mechanisms behind the effectiveness of SFRT have been attributed to certain bystander effects and abscopal effects, such as the radiation-mediated anti-tumor immunity (16)(17)(18)(19)(20)(21)(22)(23) or perfusion modulation (10,24). The key characteristics of SFRT in either GRID or LRT configurations is the Peak-Valley dose distribution, where high dose of radiation is delivered to the peaks or vertices, leaving relatively lower dose in the valleys (between the peaks or vertices) (9-15).…”

LITE SABR M1: a Phase I Trial of Lattice Stereotactic Body Radiotherapy for Large Tumors

“…Lattice radiotherapy) that simultaneously delivers a conformal lower dose of radiation to a planning target volume (PTV) with a simultaneous integrated boost to a geometric lattice of spherical sub-volumes confined to gross tumor. 11 Both GRID and Lattice radiotherapy have been used as definitive treatment, as a boost after conventional radiation, and de novo or for reirradiation. While the literature has been limited to retrospective studies, GRID and Lattice have associated with significant clinical responses and limited toxicities in large and/or radioresistant tumors, including non-small cell lung cancer and sarcomas.…”