Clinical aspects of spatially fractionated radiation therapy treatments.

To provide clinical guidance for centers wishing to implement photon spatially fractionated radiation therapy (SFRT) treatments using either a brass grid or volumetric modulated arc therapy (VMAT) lattice approach. We describe in detail processes which have been developed over the course of a 3-year period during which our institution treated over 240 SFRT cases. The importance of patient selection, along with aspects of simulation, treatment planning, quality assurance, and treatment delivery are discussed. Illustrative examples involving clinical cases are shown, and we discuss safety implications relevant to the heterogeneous dose distributions. SFRT can be an effective modality for tumors which are otherwise challenging to manage with conventional radiation therapy techniques or for patients who have limited treatment options. However, SFRT has several aspects which differ drastically from conventional radiation therapy treatments. Therefore, the successful implementation of an SFRT treatment program requires the multidisciplinary expertise and collaboration of physicians, physicists, dosimetrists, and radiation therapists. We have described methods for patient selection, simulation, treatment planning, quality assurance and delivery of clinical SFRT treatments which were built upon our experience treating a large patient population with both a brass grid and VMAT lattice approach. Preclinical research and patient trials aimed at understanding the mechanism of action are needed to elucidate which patients may benefit most from SFRT, and ultimately expand its use.

Grams MP ，Deufel CL ，Kavanaugh JA ，Corbin KS ，Ahmed SK ，Haddock MG ，Lester SC ，Ma DJ ，Petersen IA ，Finley RR ，Lang KG ，Spreiter SS ，Park SS ，Owen D ... -  《-》

Which Modality of SFRT Should be Considered First for Bulky Tumor Radiation Therapy, GRID or LATTICE?

Spatially fractionated radiation therapy (SFRT), also known as the GRID and LATTICE radiotherapy (GRT, LRT), the concept of treating tumors by delivering a spatially modulated dose with highly non-uniform dose distributions, is a treatment modality of growing interest in radiation oncology, physics, and radiation biology. Clinical experience in SFRT has suggested that GRID and LATTICE therapy can achieve a high response and low toxicity in the treatment of refractory and bulky tumors. Limited initially to GRID therapy using block collimators, advanced, and versatile multi-leaf collimators, volumetric modulated arc technologies and particle therapy have since increased the capabilities and individualization of SFRT and expanded the clinical investigation of SFRT to various dosing regimens, multiple malignancies, tumor types and sites. As a 3D modulation approach outgrown from traditional 2D GRID, LATTICE therapy aims to reconfigure the traditional SFRT as spatial modulation of the radiation is confined solely to the tumor volume. The distinctively different beam geometries used in LATTICE therapy have led to appreciable variations in dose-volume distributions, compared to GRID therapy. The clinical relevance of the variations in dose-volume distribution between LATTICE and traditional GRID therapies is a crucial factor in determining their adoption in clinical practice. In this Point-Counterpoint contribution, the authors debate the pros and cons of GRID and LATTICE therapy. Both modalities have been used in clinics and their applicability and optimal use have been discussed in this article.

Zhang H ，Wu X 《-》

Assessing dosimetric advancements in spatially fractionated radiotherapy: From grids to lattices.

Spatially fractionated radiotherapy (SFRT) techniques have undergone transformative evolution, encompassing physical GRID therapy, MLC-based grids, virtual TOMO GRIDs, and 3-dimensional high-dose lattices. Historical roots trace back to Alban Köhler's pioneering Spatially fractionated grid therapy (SFGRT), utilizing physical grids for dose modulation. Technological innovations introduced multi-leaf collimators (MLCs), enabling adaptable spatial fractionation and a shift to the broader term "SFRT." Physics and dosimetry-based studies have demonstrated the feasibility of computerized treatment planning and identified the potential to minimize the peripheral dose while using such high-dose therapy. Meanwhile, 3-dimensional high-dose lattices showed enhanced precision. The meticulous placement of high-dose volumetric spheres enables a reduction in the volume of high-dose spills. Advancements in 3-dimensional lattices through intensity-modulated radiotherapy and volumetric modulated arc therapy (VMAT) techniques offer enhanced therapeutic options. A database of SFRT studies identified 723 articles. This review shows the trajectory of SFRT from traditional grids to MLC-based approaches, virtual TOMO GRIDs, and innovative 3-dimensional lattices. Technological innovations, dosimetric advancements, and clinical feasibility have underscored the continual progress in refining spatially fractionated radiotherapy. The integration of MLCs and lattice techniques has demonstrated improved therapeutic outcomes, solidifying their relevance in modern radiation therapy protocols. Research has yet to reveal a clear correlation between treatment outcomes and dosimetric parameters. Additional investigations are necessary to assess the impact of various dosimetric parameters, such as EUD, peak-to-valley ratio (PVDR), D5%, D10%, D20%, D90%, etc., on the effectiveness of treatments.

At B ，Velayudham R 《-》

Overview and Recommendations for Prospective Multi-institutional Spatially Fractionated Radiation Therapy Clinical Trials.

Li H ，Mayr NA ，Griffin RJ ，Zhang H ，Pokhrel D ，Grams M ，Penagaricano J ，Chang S ，Spraker MB ，Kavanaugh J ，Lin L ，Sheikh K ，Mossahebi S ，Simone CB ，Roberge D ，Snider JW ，Sabouri P ，Molineu A ，Xiao Y ，Benedict SH ... -  《-》

Spatially Fractionated Radiotherapy in the Era of Immunotherapy.

Spatially fractionated radiotherapy (SFRT) includes historical grid therapy approaches but more recently encompasses the controlled introduction of one or more cold dose regions using intensity modulation delivery techniques. The driving hypothesis behind SFRT is that it may allow for an increased immune response that is otherwise suppressed by radiation effects. With both two- and three-dimensional SFRT approaches, SFRT dose distributions typically include multiple dose cold spots or valleys. Despite its unconventional methods, reported clinical experience shows that SFRT can sometimes induce marked tumor regressions, even in patients with large hypoxic tumors. Preclinical models using extreme dose distributions (i.e., half-sparing) have been shown to nevertheless result in full tumor eradications, a more robust immune response, and systemic anti-tumor immunity. SFRT takes advantage of the complementary immunomodulatory features of low- and high-dose radiotherapy to integrate the delivery of both into a single target. Clinical trials using three-dimensional SFRT (i.e., lattice-like dose distributions) have reported both promising tumor and toxicity results, and ongoing clinical trials are investigating synergy between SFRT and immunotherapies.

McMillan MT ，Khan AJ ，Powell SN ，Humm J ，Deasy JO ，Haimovitz-Friedman A ... -  《-》