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Purpose: To investigate the effect of interplay between spot-scanning proton beams and respiration-induced tumor motion on internal target volume coverage for pediatric patients. Materials and Methods: Photon treatments for 10 children with representative tumor motions (1–13 mm superior-inferior) were replanned to simulate single-field uniform dose- optimized proton therapy. Static plans were designed by using average computed tomography (CT) data sets created from 4D CT data to obtain nominal dose distributions. The motion interplay effect was simulated by assigning each spot in the static plan delivery sequence to 1 of 10 respiratory-phase CTs, using the actual patient breathing trace and specifications of a synchrotron-based proton system. Dose distributions for individual phases were deformed onto the space of the average CT and summed to produce the accumulated dose distribution, whose dose-volume histogram was compared with the one from the static plan. Results: Tumor motion had minimal impact on the internal target volume hot spot (D2), which deviated by <3% from the nominal values of the static plans. The cold spot (D98) was also minimally affected, except in 2 patients with diaphragmatic tumor motion exceeding 10 mm. The impact on tumor coverage was more pronounced with respect to the V99 rather than the V95. Decreases of 10% to 49% in the V99 occurred in multiple patients for whom the beam paths traversed the lung-diaphragm interface and were, therefore, more sensitive to respiration-induced changes in the water equivalent path length. Fractionation alone apparently did not mitigate the interplay effect beyond 6 fractions. Conclusion: The interplay effect is not a concern when delivering scanning proton beams to younger pediatric patients with tumors located in the retroperitoneal space and tumor motion of <5 mm. Children and adolescents with diaphragmatic tumor motion exceeding 10 mm require special attention, because significant declines in target coverage and dose homogeneity were seen in simulated treatments of such patients.

Purpose Despite the success of fractionation in clinical practice to spare healthy tissue, it remains common for mouse models used to study the efficacy of radiation therapy to use minimal or no fractionation. The goal of our study was to create a fractionated mouse model of radiation necrosis that we could compare to our single fraction model. Methods Precision X-Ray’s X-Rad 320 cabinet irradiator was used to irradiate the cerebrum of mice with four different fractionation schemes, while a 7 T Bruker magnetic resonance imaging (MRI) scanner using T2 and post-contrast T1 imaging was used to track the development of radiation necrosis over the span of six weeks. Results All four fractionation schemes with single fraction equivalent doses (SFED) less than 50 Gy for the commonly accepted alpha/beta ratio (α/β) value of 2–3 Gy produced radiation necrosis comparable to what would be achieved with single fraction doses of 80 and 90 Gy. This is surprising when previous work using single fractions of 50 Gy produced no visible radiation necrosis, with the results of this study showing fractionation not sparing brain tissue as much as expected. Conclusion Further interpretation of these results must take into consideration other studies which have shown a lack of sparing when fractionation has been incorporated, as well as consider factors such as the use of large doses per fraction, the time between fractions, and the limitations of using a murine model to analyze the human condition.

Background: Murine models are among the most common type of preclinical animal models used to study the human condition, but a wide selection of different mice is currently in use with these differences potentially compromising study results and impairing the ability to reconcile interstudy results. Our goal was to determine how the strain and sex of the mice selection would affect the development of radiation necrosis in our murine model of radiation-induced cerebral necrosis. Methods: We generated this model by using a preclinical irradiator to irradiate a sub-hemispheric portion of the brain of mice with single-fraction doses of 80 Gy. Eight possible combinations of mice made up of two different with two substrains each (BALB/cN, BALB/cJ, C57BL/6 N, and C57BL/6 J) and both sexes were irradiated in this study. Radiation necrosis development was tracked up to 8 weeks with a 7 T Bruker MRI utilizing T2-weighted and postcontrast T1-weighted imaging. MRI results were compared to and validated with the use of histology which utilized a scale from 0 to 3 in ascending order of damage. Results: Both time post-irradiation and strain (BALB/c vs C57BL/6) were significant factors affecting radiation necrosis development. Sex was in general not a statistically significant parameter in terms of radiation necrosis development. Conclusion: Mouse strain thus needs to be considered when evaluating the results of necrosis models. However, sex does not appear to be a variable needing major consideration.