This paper summarizes clinical commissioning of the world's first commercial, clinically utilized installation of a compact, image‐guided, pencil‐beam scanning, intensity‐modulated proton therapy system, the IBA Proteus® ONE, at the Willis‐Knighton Cancer Center (WKCC) in Shreveport, LA. The Proteus® ONE is a single‐room, compact‐gantry system employing a cyclotron‐generated proton beam with image guidance via cone‐beam CT as well as stereoscopic orthogonal and oblique planar kV imaging. Coupling 220° of gantry rotation with a 6D robotic couch capable of in plane patient rotations of over 180° degrees allows for 360° of treatment access. Along with general machine characterization, system commissioning required: (a) characterization and calibration of the proton beam, (b) treatment planning system commissioning including CT‐to‐density curve determination, (c) image guidance system commissioning, and (d) safety verification (interlocks and radiation survey). System readiness for patient treatment was validated by irradiating calibration TLDs as well as prostate, head, and lung phantoms from the Imaging and Radiation Oncology Core (IROC), Houston. These results confirmed safe and accurate machine functionality suitable for patient treatment. WKCC also successfully completed an on‐site dosimetry review by an independent team of IROC physicists that corroborated accurate Proteus® ONE dosimetry.

An image-based skeletal dosimetry model for internal electron sources was created for the ICRP-defined reference adult female. Many previous skeletal dosimetry models, which are still employed in commonly used internal dosimetry software, do not properly account for electron escape from trabecular spongiosa, electron cross-fire from cortical bone, and the impact of marrow cellularity on active marrow self-irradiation. Furthermore, these existing models do not employ the current ICRP definition of a 50 µm bone endosteum (or shallow marrow). Each of these limitations was addressed in the present study. Electron transport was completed to determine specific absorbed fractions to both active and shallow marrow of the skeletal regions of the University of Florida reference adult female. The skeletal macrostructure and microstructure were modeled separately. The bone macrostructure was based on the whole-body hybrid computational phantom of the UF series of reference models, while the bone microstructure was derived from microCT images of skeletal region samples taken from a 45 years-old female cadaver. The active and shallow marrow are typically adopted as surrogate tissue regions for the hematopoietic stem cells and osteoprogenitor cells, respectively. Source tissues included active marrow, inactive marrow, trabecular bone volume, trabecular bone surfaces, cortical bone volume, and cortical bone surfaces. Marrow cellularity was varied from 10 to 100 percent for active marrow self-irradiation. All other sources were run at the defined ICRP Publication 70 cellularity for each bone site. A total of 33 discrete electron energies, ranging from 1 keV to 10 MeV, were either simulated or analytically modeled. The method of combining skeletal macrostructure and microstructure absorbed fractions assessed using MCNPX electron transport was found to yield results similar to those determined with the PIRT model applied to the UF adult male skeletal dosimetry model. Calculated skeletal averaged absorbed fractions for each source-target combination were found to follow similar trends of more recent dosimetry models (image-based models) but did not follow results from skeletal models based upon assumptions of an infinite expanse of trabecular spongiosa.

Glioblastoma (GBM) has a poor prognosis despite intensive treatment with surgery and chemoradiotherapy. Previous studies using dose-escalated radiotherapy have demonstrated improved survival; however, increased rates of radionecrosis have limited its use. Development of radiosensitizers could improve patient outcome. In the present study, we report the use of sodium sulfide (Na 2 S), a hydrogen sulfide (H 2 S) donor, to selectively kill GBM cells (T98G and U87) while sparing normal human cerebral microvascular endothelial cells (hCMEC/D3). Na 2 S also decreased mitochondrial respiration, increased oxidative stress and induced γH2AX foci and oxidative base damage in GBM cells. Since Na 2 S did not significantly alter T98G capacity to perform non-homologous end-joining or base excision repair, it is possible that GBM cell killing could be attributed to increased damage induction due to enhanced reactive oxygen species production. Interestingly, Na 2 S enhanced mitochondrial respiration, produced a more reducing environment and did not induce high levels of DNA damage in hCMEC/D3. Taken together, this data suggests involvement of mitochondrial respiration in Na 2 S toxicity in GBM cells. The fact that survival of LN-18 GBM cells lacking mitochondrial DNA (ρ 0 ) was not altered by Na 2 S whereas the survival of LN-18 ρ + cells was compromised supports this conclusion. When cells were treated with Na 2 S and photon or proton radiation, GBM cell killing was enhanced, which opens the possibility of H 2 S being a radiosensitizer. Therefore, this study provides the first evidence that H 2 S donors could be used in GBM therapy to potentiate radiation-induced killing.

Efforts to assess in utero radiation doses and related quantities to the developing fetus should account for the presence of the surrounding maternal tissues. Maternal tissues can provide varying levels of protection to the fetus by shielding externally-emitted radiation or, alternatively, can become sources of internally-emitted radiation following the biokinetic uptake of medically-administered radiopharmaceuticals or radionuclides located in the surrounding environment--as in the case of the European Union's SOLO project (Epidemiological Studies of Exposed Southern Urals Populations). The University of Florida had previously addressed limitations in available computational phantom representation of the developing fetus by constructing a series of hybrid computational fetal phantoms at eight different ages and three weight percentiles. Using CT image sets of pregnant patients contoured using 3D-DOCTOR(TM), the eight 50th percentile fetal phantoms from that study were systematically combined in Rhinoceros(TM) with the UF adult non-pregnant female to yield a series of reference pregnant female phantoms at fetal ages 8, 10, 15, 20, 25, 30, 35 and 38 weeks post-conception. Deformable, non-uniform rational B-spline surfaces were utilized to alter contoured maternal anatomy in order to (1) accurately position and orient each fetus and surrounding maternal tissues and (2) match target masses of maternal soft tissue organs to reference data reported in the literature.

Historically, the development of computational phantoms for radiation dosimetry have primarily been directed at capturing and representing adult and pediatric anatomy, with less emphasis devoted to models of the human fetus. As concern grows over possible radiation-induced cancers from medical and non-medical exposures of the pregnant female, the need to better quantify fetal radiation doses, particularly at the organ-level, also increases. Studies such as the European Union’s SOLO (Epidemiological Studies of Exposed Southern Urals Populations) hope to improve our understanding of cancer risks following chronic in-utero radiation exposure. For projects like SOLO, currently available fetal anatomic models do not provide sufficient anatomical detail for organ-level dose assessment. To address this need, two fetal hybrid computational phantoms were constructed using high-quality magnetic resonance imaging (MRI) and computed tomography (CT) image sets obtained for two well-preserved fetal specimens aged 11.5 and 21 weeks post-conception. Individual soft tissue organs, bone sites, and outer body contours were segmented from these images using 3D-DOCTORTM and then imported to the 3D modeling software package RhinocerosTM for further modeling and conversion of soft tissue organs, certain bone sites, and outer body contours to deformable non-uniform rational B-spline (NURBS) surfaces. The two specimen-specific phantoms, along with a modified version of the 38-week UF hybrid newborn phantom, comprised a set of base phantoms from which a series of hybrid computational phantoms was derived for fetal ages 8, 10, 15, 20, 25, 30, 35 and 38 weeks post-conception. The methodology used to construct the series of phantoms accounted for the following age-dependent parameters: (1) variations in skeletal size and proportion, (2) bone-dependent variations in relative levels of bone growth, (3) variations in individual organ masses and total fetal masses and (4) statistical percentile variations in skeletal size, individual organ masses, and total fetal masses. The resulting series of fetal hybrid computational phantoms is applicable to organ-level and bone-level internal and external radiation dosimetry for human fetuses of various ages and weight percentiles.