Outcomes of Spatially Fractionated Radiotherapy (GRID) for Bulky Soft Tissue Sarcomas in a Large Animal Model

Abstract

GRID directs alternating regions of high- and low-dose radiation at tumors. A large animal model mimicking the geometries of human treatments is needed to complement existing rodent systems (eg, microbeam) and clarify the physical and biological attributes of GRID. A pilot study was undertaken in pet dogs with spontaneous soft tissue sarcomas to characterize responses to GRID. Subjects were treated with either 20 Gy (3 dogs) or 25 Gy (3 dogs), delivered using 6 MV X-rays and a commercial GRID collimator. Acute toxicity and tumor responses were assessed 2, 4, and 6 weeks later. Acute Radiation Therapy Oncology Group grade I skin toxicity was observed in 3 of the 6 dogs; none experienced a measurable response, per Response Evaluation Criteria in Solid Tumors. Serum vascular endothelial growth factor, tumor necrosis factor α, and secretory sphingomyelinase were assayed at baseline, 1, 4, 24, and 48 hours after treatment. There was a trend toward platelet-corrected serum vascular endothelial growth factor concentration being lower 1 and 48 hours after GRID than at baseline. There was a significant decrease in secretory sphingomyelinase activity 48 hours after 25 Gy GRID (P = .03). Serum tumor necrosis factor α was quantified measurable at baseline in 4 of the 6 dogs and decreased in each of those subjects at all post-GRID time points. The new information generated by this study includes the observation that high-dose, single fraction application of GRID does not induce measurable reduction in volume of canine soft tissue sarcomas. In contrast to previously published data, these data suggest that GRID may be associated with at least short-term reduction in serum concentration of vascular endothelial growth factor and serum activity of secretory sphingomyelinase. Because GRID can be applied safely, and these tumors can be subsequently surgically resected as part of routine veterinary care, pet dogs with sarcomas are an appealing model for studying the radiobiologic responses to spatially fractionated radiotherapy.

Biological Guided Carbon-Ion Microporous Radiation to Tumor Hypoxia Area Triggers Robust Abscopal Effects as Open Field Radiation

“…Recently, the results of a growing number of in vitro and in vivo studies indicate that, in addition to the local therapeutic effects, radiation therapy may be in favor of changing the tumor microenvironments correlated with immunity and endothelial cells of the tumor micro-vasculatures, thereby inducing the nontarget effects, such as radiation induced bystander effects and abscopal effects (RIAEs) (10)(11)(12)(13). RIAEs are radiation induced effects in unirradiated tumors distant from irradiated target regresses.…”

Technical Note: Dosimetric feasibility of lattice radiotherapy for breast cancer using GammaPod

“…The skin was contoured from the surface to 5 mm depth. A total of 20 Gy was used for average skin dose evaluation since, in GRID therapy, typically, a higher skin dose than the prescribed dose is acceptable regardless of the possibility of acute skin toxicity 9,22 . It turns out that our GammaPod‐based LRT simulations yielded an average skin dose similar to valley dose, and, therefore, greatly reduced the chances of additional skin complications.…”

Definitive radiotherapy in the management of non-resectable or residual retroperitoneal sarcomas: institutional cohort analysis and systematic review

“…Either increase or decrease in size might be observed, as in a study by Haas et al (2019) on extremity STS, changes in size during preoperative RT occurred in 58 out of 99 cases and in 41 of them increase was noted, while RT plan had to be adapted in eight cases [35]. Advanced RT delivery and planning techniques resulted in development of several approaches to the treatment of bulky tumors, such as spatially fractionated radiation therapy applied through sieve-like collimators, a so-called GRID therapy [37]. GRID further evolved into 3-D Lattice RT technique that restricts the highdose regions to tumor volume [38].…”