PSOR03  Presentation Time: 4:40 PM: A 3-D Printed Platform for Preclinical In Vitro Studies Incorporating Clinically Relevant HDR and External Beam Therapy Workflows

Purpose Current preclinical in vitro brachytherapy studies predominantly rely on low dose rate, orthovoltage x−ray irradiators which lack the dosimetric characteristics of clinical irradiators. A 3D−printed platform for performing in vitro tissue culture studies using a clinical HDR brachytherapy afterloader was designed to allow variable distances between the HDR source and the cells to vary the dose rate resulting in clinically relevant dose distributions. The platform allows for maximization of the instantaneous dose rate in order to investigate radiobiological response in regions of high dose rates proximal to the 192Ir source while being easily adaptable to other clinically relevant source−to−target distances as well as multi−modality studies including external beam devices. A standard clinical treatment planning and delivery workflow can be used, including commercial model−based dose calculation algorithms (MBDCA) to account for heterogeneities. Materials and Methods The platform was designed and printed using a fused deposition modeling 3D printer (Ultimaker, Utrecht, Netherlands) with a polylactic acid filament. To assess the dosimetry of the platform, CT−based treatment plans of a 96−well standard tissue culture plate (Techno Plastic Products, Trasadingen, Switzerland) were created using BrachyVision or Eclipse (both Varian Medical Systems, Palo Alto, CA). Dosimetry for HDR brachytherapy was calculated using homogeneous water−based dose calculations (TG−43) and an MBDCA (Acuros BV), while external beam dosimetry was calculated using a commercial convolution/superposition algorithm (AAA) and an MBDCA (AXB). Brachytherapy dosimetry was verified at a source−to−cell distance of 1 cm and immediately proximal to the source using EBT3 (Radiation Products Design Incorporation, Albertville, MN) film and/or nanoDot™ (Landauer, Glenwood, IL) optically stimulated luminescent dosimeters (OSLDs). Results At 1 cm and 4 mm (adjacent) from the source to the adherent layer of cells, calculated dose differences for a 4 Gy uniform field between TG−43 and MBDCA calculations were 8% and 2.8%, respectively. Within a well at 1 cm, the mean standard deviations for TG−43 and MBDCA calculations were 0.21% and 0.35%, respectively, and adjacent to the source were 1.63% and 2.05%, respectively. The calculated dose difference for a uniform field between AAA and AXB calculations in the external beam plan was 2.4%. The mean standard deviations within a well for AAA and AXB calculations were 2.13% and 0.52%, respectively. At 1 cm, the average (± standard deviation) 2D gamma passing rates on film were 94.8±1.9% and 98±0.9% for TG−43 and MBDCA calculations, respectively, using a 5%/2mm criteria. Immediately adjacent to the source, OSLD measurements resulted in average percent differences of 10.7±3% and 10.3±4%, and average distances−to−agreement of 1.2±0.4 mm and 1.4±0.4 mm for TG−43 and MBDCA calculations, respectively. Conclusion The platform allows for the delivery of HDR brachytherapy doses in regions of high dose−rate while also being adaptable to other experimental setups and multi−modality studies, addressing some of the current limitations in pre−clinical brachytherapy research. In the absence of backscatter, as seen with the 96−well plate, dose calculation algorithms employing heterogeneity corrections are recommended regardless of modality. This study indicates in vitro studies using clinically−relevant HDR brachytherapy and external beam therapy workflows and dose delivery are feasible with this platform. Current preclinical in vitro brachytherapy studies predominantly rely on low dose rate, orthovoltage x−ray irradiators which lack the dosimetric characteristics of clinical irradiators. A 3D−printed platform for performing in vitro tissue culture studies using a clinical HDR brachytherapy afterloader was designed to allow variable distances between the HDR source and the cells to vary the dose rate resulting in clinically relevant dose distributions. The platform allows for maximization of the instantaneous dose rate in order to investigate radiobiological response in regions of high dose rates proximal to the 192Ir source while being easily adaptable to other clinically relevant source−to−target distances as well as multi−modality studies including external beam devices. A standard clinical treatment planning and delivery workflow can be used, including commercial model−based dose calculation algorithms (MBDCA) to account for heterogeneities. The platform was designed and printed using a fused deposition modeling 3D printer (Ultimaker, Utrecht, Netherlands) with a polylactic acid filament. To assess the dosimetry of the platform, CT−based treatment plans of a 96−well standard tissue culture plate (Techno Plastic Products, Trasadingen, Switzerland) were created using BrachyVision or Eclipse (both Varian Medical Systems, Palo Alto, CA). Dosimetry for HDR brachytherapy was calculated using homogeneous water−based dose calculations (TG−43) and an MBDCA (Acuros BV), while external beam dosimetry was calculated using a commercial convolution/superposition algorithm (AAA) and an MBDCA (AXB). Brachytherapy dosimetry was verified at a source−to−cell distance of 1 cm and immediately proximal to the source using EBT3 (Radiation Products Design Incorporation, Albertville, MN) film and/or nanoDot™ (Landauer, Glenwood, IL) optically stimulated luminescent dosimeters (OSLDs). At 1 cm and 4 mm (adjacent) from the source to the adherent layer of cells, calculated dose differences for a 4 Gy uniform field between TG−43 and MBDCA calculations were 8% and 2.8%, respectively. Within a well at 1 cm, the mean standard deviations for TG−43 and MBDCA calculations were 0.21% and 0.35%, respectively, and adjacent to the source were 1.63% and 2.05%, respectively. The calculated dose difference for a uniform field between AAA and AXB calculations in the external beam plan was 2.4%. The mean standard deviations within a well for AAA and AXB calculations were 2.13% and 0.52%, respectively. At 1 cm, the average (± standard deviation) 2D gamma passing rates on film were 94.8±1.9% and 98±0.9% for TG−43 and MBDCA calculations, respectively, using a 5%/2mm criteria. Immediately adjacent to the source, OSLD measurements resulted in average percent differences of 10.7±3% and 10.3±4%, and average distances−to−agreement of 1.2±0.4 mm and 1.4±0.4 mm for TG−43 and MBDCA calculations, respectively. The platform allows for the delivery of HDR brachytherapy doses in regions of high dose−rate while also being adaptable to other experimental setups and multi−modality studies, addressing some of the current limitations in pre−clinical brachytherapy research. In the absence of backscatter, as seen with the 96−well plate, dose calculation algorithms employing heterogeneity corrections are recommended regardless of modality. This study indicates in vitro studies using clinically−relevant HDR brachytherapy and external beam therapy workflows and dose delivery are feasible with this platform.