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Comparison between average CT planned and CBCT recalculated dose metrics (Gy) for the target structures. All doses are reported as means [standard deviation] in units of Gy

Time to reach 2-times starting tumor volume (TGTV2) increases linearly with increasing uniform radiation dose.

An example of distribution of hypoxia tracer HX4 (3 hours post injection) and FDG (2 hours post injection) in the same rhabdomyosarcoma bearing rat 20 hours apart, demonstrating large overlap between the tracers. White contours correspond to 30% of the GTV (magenta contours) with the highest SUV. Dice similarity coefficient is 0.79 for this example.

Experimental design. Hot Boost (Cold Boost ) 40% (60%) indicates 40% (60%) higher radiation dose to tumor sub-volume with the highest (lowest) FDG uptake than to the rest of the tumor.

Purpose: We tested therapeutic efficacy of two dose painting strategies of applying higher radiation dose to tumor subvolumes with high FDG uptake (biologic target volume, BTV): dose escalation and dose redistribution. We also investigated whether tumor response was determined by the highest dose in BTV or the lowest dose in gross tumor volume (GTV).Experimental Design: FDG uptake was evaluated in rat rhabdomyosarcomas prior to irradiation. BTV was defined as 30% of GTV with the highest (BTVhot) or lowest (BTVcold) uptake. To test efficacy of dose escalation, tumor response (time to reach two times starting tumor volume, TGTV2) to Hot Boost irradiation (40% higher dose to BTVhot) was compared with Cold Boost (40% higher dose to BTVcold), while mean dose to GTV remained 12 Gy. To test efficacy of dose redistribution, TGTV2 after Hot Boost was compared with uniform irradiation with the same mean dose (8 or 12 Gy).Results: TGTV2 after 12 Gy delivered heterogeneously (Hot and Cold Boost) or uniformly were not significantly different: 20.2, 19.5, and 20.6 days, respectively. Dose redistribution (Hot Boost) with 8 Gy resulted in faster tumor regrowth as compared with uniform irradiation (13.3 vs. 17.1 days; P = 0.026). Further increase in dose gradient to 60% led to a more pronounced decrease in TGTV2 (10.9 days; P < 0.0001).Conclusions: Dose escalation effect was independent of FDG uptake in target tumor volume, while dose redistribution was detrimental in this tumor model for dose levels applied here. Our data are consistent with the hypothesis that tumor response depends on the minimum intratumoral dose. Clin Cancer Res; 21(24); 5511–8. ©2015 AACR.