Abstract LB-359: Effects of space time fractionated radiation on normal tissue toxicity
Authors: Wu Xiaodong , Gupta Seema , Umar Saleem , Agarwal Alok K. , Pollack Alan , Ahmed Mansoor M. 
Published: August 2014

Abstract
Purpose: Space-Time Fractionation (STF) proposed herein is a novel concept based on the long-standing clinical data of Spatially Fractionated GRID Radiotherapy. The conventional GRID therapy, or the recently proposed LATTICE therapy is generally intended for single-fraction treatment. The STF extends the concept to definitive, fractionated radiation therapy, aiming at maximum tumor control with significantly reduced normal tissue toxicity.
Methods: In this fractionation scheme, treatment volume was divided into segments or slices, consecutively numbered 1,2,3,4,5,6,7,8…, with typical slice thickness of 1–2 cm. This formed the spatially fractionated structure. Alternated time fraction numbers (time fractionation), were delivered to their corresponding spatial segments, i.e., the odd fractions 1,3,5,7,9, … were delivered to spatial slices 1,3,5,7… and the even fractions 2,4,6,8,… were delivered to spatial slices 2,4,6,8. To demonstrate the normal tissue sparing effect, three groups of C57/BL6 mice (16/group) were used: untreated (UT); STF, 500cGy/fx × 10 (5x Position 1 + 5x Position 2) delivered through a block of multiple equally spaced open/closed slits of 2 mm width; Conventional 310cGy × 10, open field. The two irradiated groups having the same biological equivalent dose (BED) delivered to the whole abdomen. Two mice were sacrificed immediately, 24h and 7 days after radiation and intestines, kidneys and liver tissues were collected. The formalin fixed tissues were stained with hematoxylin and eosin and pathological analysis was carried out to assess the damage. Remaining mice were followed for overall survival.
Results: Although mice from all the treatment groups survived for at least 90 days after the treatment, pathological analysis of the tissues clearly showed maximal damage with open field irradiation compared to STF. Intestinal epithelial cells from open field irradiated mice showed severe damage with cell loss in intestinal crypts and thus villi were shortened and blunted. Even one month after irradiation, amphophilic cytoplasm, variation in the size of the nuclei, clumping of chromatin and prominent nucleoli were observed in the intestinal tissues. Number of mitotic figures increased with time indicating regeneration but recovery was only partial. In case of the STF irradiated mice, negligible damage was observed at all the time points studied. Again, kidney tissues obtained from open field irradiated mice showed highly disorganized tubule cells structure compared to kidney tissue from mice subjected to STF. Currently, we are assessing the effects in the liver tissue.
Conclusions: Results show that STF could be a new approach in treating advanced/recurrent cancers with improved local tumor control without increasing normal tissue toxicity.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-359. doi:10.1158/1538-7445.AM2011-LB-359