RESUMEN
Purpose: Animal studies with ultrahigh dose-rate radiation therapy (FLASH, >40 Gy/s) preferentially spare normal tissues without sacrificing antitumor efficacy compared with conventional dose-rate radiation therapy (CONV). At the University of Washington, we developed a cyclotron-generated preclinical scattered proton beam with FLASH dose rates. We present the technical details of our FLASH radiation system and preliminary biologic results from whole pelvis radiation. Methods and Materials: A Scanditronix MC50 compact cyclotron beamline has been modified to produce a 48.7 MeV proton beam at dose rates between 0.1 and 150 Gy/s. The system produces a 6 cm diameter scattered proton beam (flat to ± 3%) at the target location. Female C57BL/6 mice 5 to 6 weeks old were used for all experiments. To study normal tissue effects in the distal colon, mice were irradiated using the entrance region of the proton beam to the whole pelvis, 18.5 Gy at different dose rates: control, CONV (0.6-1 Gy/s) and FLASH (50-80 Gy/s). Survival was monitored daily and EdU (5-ethynyl-2´-deoxyuridine) staining was performed at 24- and 96-hours postradiation. Cleaved caspase-3 staining was performed 24-hours postradiation. To study tumor control, allograft B16F10 tumors were implanted in the right flank and received 18 Gy CONV or FLASH proton radiation. Tumor growth and survival were monitored. Results: After 18.5 Gy whole pelvis radiation, survival was 100% in the control group, 0% in the CONV group, and 44% in the FLASH group (P < .01). EdU staining showed cell proliferation was significantly higher in the FLASH versus CONV group at both 24-hours and 96-hours postradiation in the distal colon, although both radiation groups showed decreased proliferation compared with controls (P < .05). Lower cleaved caspase-3 staining was seen in the FLASH versus conventional group postradiation (P < .05). Comparable flank tumor control was observed in the CONV and FLASH groups. Conclusions: We present our preclinical FLASH proton radiation system and biologic results showing improved survival after whole pelvis radiation, with equivalent tumor control.
RESUMEN
The objective of this study was to confirm the feasibility of three-dimensionally-printed (3D-printed), personalized whole-body anthropomorphic phantoms for radiation dose measurements in a variety of charged and uncharged particle radiation fields. We 3D-printed a personalized whole-body phantom of an adult female with a height of 154.8 cm, mass of 90.7 kg, and body mass index of 37.8 kg/m2. The phantom comprised of a hollow plastic shell filled with water and included a watertight access conduit for positioning dosimeters. It is compatible with a wide variety of radiation dosimeters, including ionization chambers that are suitable for uncharged and charged particles. Its mass was 6.8 kg empty and 98 kg when filled with water. Watertightness and mechanical robustness were confirmed after multiple experiments and transportations between institutions. The phantom was irradiated to the cranium with therapeutic beams of 170-MeV protons, 6-MV photons, and fast neutrons. Radiation absorbed dose was measured from the cranium to the pelvis along the longitudinal central axis of the phantom. The dose measurements were made using established dosimetry protocols and well-characterized instruments. For the therapeutic environments considered in this study, stray radiation from intracranial treatment beams was the lowest for proton therapy, intermediate for photon therapy, and highest for neutron therapy. An illustrative example set of measurements at the location of the thyroid for a square field of 5.3 cm per side resulted in 0.09, 0.59, and 1.93 cGy/Gy from proton, photon, and neutron beams, respectively. In this study, we found that 3D-printed personalized phantoms are feasible, inherently reproducible, and well-suited for therapeutic radiation measurements. The measurement methodologies we developed enabled the direct comparison of radiation exposures from neutron, proton, and photon beam irradiations.
