Radio-Immune Response of Spatially Fractionated Radiotherapy for VMAT Lattice Plans

Purpose/Objective(s)To evaluate radio-immune response of spatially fractionated radiotherapy (SFRT) for large tumors using VMAT Lattice technique in terms of tumor volume under irradiation and dose fractionation schemes after SFRT.Materials/MethodsEleven patients treated with SFRT from a single institution were retrospectively replanned to deliver 15Gy in single fraction using Lattice technique. High dose regions are defined by multiple spheres with the diameter of 1.25 to 1.5cm and their vertex space of 3.0 to 4.0cm inside of GTV. VMAT plans with multiple arcs were developed for SFRT. Four palliative fractionation regimens of 200cGy x 12 (EQD2 = 24Gy with a/b of 10Gy), 400cGy x 5 (23.3Gy), 600cGy x 3 (24Gy) and 800cGy x2 (24Gy) and four definitive regimens of 200cGy x 24 (EQD2 = 48Gy), 400cGy x 10 (46.7Gy), 600cGy x 6 (48Gy) and 800cGy x 4 (48Gy) were considered for radiotherapy to follow SFRT. Linear quadratic (LQ) model is compared with radio-immune (RI) response model in which the activation of cytotoxic T lymphocytes, tumor immune suppression capability and immunotherapy drugs can be considered. Tumor regrowth time (TRT, time to tumor regrowth to the original volume after treatment) from each model was compared as a measure of benefit achieved from the application of SFRT.ResultsThe average volume of GTVs in this study was 776cc (range 58-2944cc). Three different SFRT plans (2D GRID technique with conventional collimator, 2D GRID with step & shoot IMRT, and 3D Lattice) were developed for each patient but only Lattice plans were considered in this study since they produced comparable dose modulation inside the tumor but only Lattice significantly reduced skin and critical organ dose. Radio-immune response model always expects longer TRT than LQ model. For palliative regimens, TRT of RI model is longer than that of LQ model by 14.5±9.9, 15.1±10.6, 17.2±12.4, 17.5±12.8 days for each fractionation scheme. When Lattice plan of 15Gy is delivered before the palliative treatment, the difference becomes 25.9±15.3, 31.5±23.3, 36.7±27.6, 37.5±28.5 days. The benefit of SFRT from RI response is only about 10-20 days. Interestingly, RI response is inversely proportional to tumor volume. When curative dose is considered, the difference of TRT is drastically changed from 25.9±9.8, 460.7±285.8, 1180.8±985.7, 1512.0±1327.5 days to 20.7±4.4, 449.0±411.7, 1725.4±2171.0, 3517.7±4531.7 days. The benefit of SFRT from RI response appears larger for large tumor with hypo-fractionation in definitive regimens.ConclusionThe benefit of SFRT is significant for large tumors with hypo fractionation in the definitive regimens when radio-immune response model is considered which is not apparent in LQ model. Radio-immune response model may help to guide the development of successful treatment scheme large tumor volumes. To evaluate radio-immune response of spatially fractionated radiotherapy (SFRT) for large tumors using VMAT Lattice technique in terms of tumor volume under irradiation and dose fractionation schemes after SFRT. Eleven patients treated with SFRT from a single institution were retrospectively replanned to deliver 15Gy in single fraction using Lattice technique. High dose regions are defined by multiple spheres with the diameter of 1.25 to 1.5cm and their vertex space of 3.0 to 4.0cm inside of GTV. VMAT plans with multiple arcs were developed for SFRT. Four palliative fractionation regimens of 200cGy x 12 (EQD2 = 24Gy with a/b of 10Gy), 400cGy x 5 (23.3Gy), 600cGy x 3 (24Gy) and 800cGy x2 (24Gy) and four definitive regimens of 200cGy x 24 (EQD2 = 48Gy), 400cGy x 10 (46.7Gy), 600cGy x 6 (48Gy) and 800cGy x 4 (48Gy) were considered for radiotherapy to follow SFRT. Linear quadratic (LQ) model is compared with radio-immune (RI) response model in which the activation of cytotoxic T lymphocytes, tumor immune suppression capability and immunotherapy drugs can be considered. Tumor regrowth time (TRT, time to tumor regrowth to the original volume after treatment) from each model was compared as a measure of benefit achieved from the application of SFRT. The average volume of GTVs in this study was 776cc (range 58-2944cc). Three different SFRT plans (2D GRID technique with conventional collimator, 2D GRID with step & shoot IMRT, and 3D Lattice) were developed for each patient but only Lattice plans were considered in this study since they produced comparable dose modulation inside the tumor but only Lattice significantly reduced skin and critical organ dose. Radio-immune response model always expects longer TRT than LQ model. For palliative regimens, TRT of RI model is longer than that of LQ model by 14.5±9.9, 15.1±10.6, 17.2±12.4, 17.5±12.8 days for each fractionation scheme. When Lattice plan of 15Gy is delivered before the palliative treatment, the difference becomes 25.9±15.3, 31.5±23.3, 36.7±27.6, 37.5±28.5 days. The benefit of SFRT from RI response is only about 10-20 days. Interestingly, RI response is inversely proportional to tumor volume. When curative dose is considered, the difference of TRT is drastically changed from 25.9±9.8, 460.7±285.8, 1180.8±985.7, 1512.0±1327.5 days to 20.7±4.4, 449.0±411.7, 1725.4±2171.0, 3517.7±4531.7 days. The benefit of SFRT from RI response appears larger for large tumor with hypo-fractionation in definitive regimens. The benefit of SFRT is significant for large tumors with hypo fractionation in the definitive regimens when radio-immune response model is considered which is not apparent in LQ model. Radio-immune response model may help to guide the development of successful treatment scheme large tumor volumes.