A proton therapy workflow based on CBCT provided clinical indicators similar to those using rCT for patients with lung cancer with considerable anatomic changes.

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The antineoplastic drug sorafenib ) is a multikinase inhibitor that targets the serine-threonine kinase B-Raf as well as several tyrosine kinases. Given the numerous molecular targets of sorafenib, there are several potential anticancer mechanisms of action, including induction of apoptosis, cytostasis, and antiangiogenesis. We observed that sorafenib has broad activity in viability assays in several human tumor cell lines but selectively induces apoptosis in only some lines. Sorafenib was found to decrease Mcl-1 levels in most cell lines tested, but this decrease did not correlate with apoptotic sensitivity. Sorafenib slows cell cycle progression and prevents irradiated cells from reaching and accumulating at G 2 -M. In synchronized cells, sorafenib causes a reversible G 1 delay, which is associated with decreased levels of cyclin D1, Rb, and phosphorylation of Rb. Although sorafenib does not affect intrinsic radiosensitivity using in vitro colony formation assays, it significantly reduces colony size. In HCT116 xenograft tumor growth delay experiments in mice, sorafenib alters radiation response in a schedule-dependent manner. Radiation treatment followed sequentially by sorafenib was found to be associated with the greatest tumor growth delay. This study establishes a foundation for clinical testing of sequential fractionated radiation followed by sorafenib in gastrointestinal and other malignancies. [Cancer Res 2007;67(19):9443-54]

This study described, developed, and tested new processing methods for reducing inaccuracies in absolute dose determination due to inhomogeneities within the film and from scanning. This study found better performance using optimized multichannel following averaging of all color channels. Combining the channel ratios in a hybrid approach also achieved high performance. Averaging the test films reduced temporal noise that severely degraded the blue channel. This methodology avoided using cumbersome, registered correction matrices. Novel registration and digital rotation of CT images enabled quantitative testing and helped improve contact between the radiochromic film and phantom.

In electron and proton radiotherapy, applications of patient‐specific electron bolus or proton compensators during radiation treatments are often necessary to accommodate patient body surface irregularities, tissue inhomogeneity, and variations in PTV depths to achieve desired dose distributions. Emerging 3D printing technologies provide alternative fabrication methods for these bolus and compensators. This study investigated the potential of utilizing 3D printing technologies for the fabrication of the electron bolus and proton compensators. Two printing technologies, fused deposition modeling (FDM) and selective laser sintering (SLS), and two printing materials, PLA and polyamide, were investigated. Samples were printed and characterized with CT scan and under electron and proton beams. In addition, a software package was developed to convert electron bolus and proton compensator designs to printable Standard Tessellation Language file format. A phantom scalp electron bolus was printed with FDM technology with PLA material. The HU of the printed electron bolus was 106.5±15.2. A prostate patient proton compensator was printed with SLS technology and polyamide material with −70.1±8.1 HU. The profiles of the electron bolus and proton compensator were compared with the original designs. The average over all the CT slices of the largest Euclidean distance between the design and the fabricated bolus on each CT slice was found to be 0.84±0.45 mm and for the compensator to be 0.40±0.42 mm. It is recommended that the properties of specific 3D printed objects are understood before being applied to radiotherapy treatments.PACS number: 81.40

Dose calculation for pencil beam scanning proton therapy requires accurate measurement of the broad tails of the proton spot profiles for every nozzle in clinical use. By applying a pair/magnification method and merging film data, 200 mm × 240 mm dose kernels extending to 10(-4) of the central spot dose are generated for six selected energies of the IBA dedicated and universal nozzles (DN and UN). One-dimensional, circular profiles up to 100 mm in radius are generated from the asymmetric profiles to facilitate spot profile comparison. For the highest energy, 225 MeV, the output of both the DN and the UN for field sizes from 40 to 200 mm increases in parallel, slowest at the surface (∼1%) and fastest at a depth of 150 mm (∼9%). In contrast, at the lowest energy, 100 MeV, the output of the DN across the same range of field sizes increases 3-4% versus 6-7% for the UN throughout all the depths. The charge deficits in the measured depth-dose of Bragg peaks are similar between the UN and the DN. At 100 MeV, the field size factor difference at the surface between two orientations of a rectangular 40 mm × 200 mm field is 1.4% at isocentre for the DN versus 2% for the UN. Though the one-dimensional distributions are similar for the primary and tail components at different positions, the primary components of the DN spots are more elliptical 270 mm upstream than at isocentre.

A major source of uncertainty in proton therapy is the conversion of Hounsfield unit (HU) to proton stopping power ratio relative to water (SPR). In this study, we measured and quantified the accuracy of a stoichiometric dual energy CT (DECT) SPR calibration. We applied a stoichiometric DECT calibration method to derive the SPR using CT images acquired sequentially at [Formula: see text] and [Formula: see text]. The dual energy index was derived based on the HUs of the paired spectral images and used to calculate the effective atomic number (Z ), relative electron density ([Formula: see text]), and SPRs of phantom and biological materials. Two methods were used to verify the derived SPRs. The first method measured the sample's water equivalent thicknesses to deduce the SPRs using a multi-layer ion chamber (MLIC) device. The second method utilized Gafchromic EBT3 film to directly compare relative ranges between sample and water after proton pencil beam irradiation. Ex vivo validation was performed using five different types of frozen animal tissues with the MLIC and three types of fresh animal tissues using film. In addition, the residual ranges recorded on the film were used to compare with those from the treatment planning system using both DECT and SECT derived SPRs. Bland-Altman analysis indicates that the differences between DECT and SPR measurement of tissue surrogates, frozen and fresh animal tissues has a mean of 0.07% and standard deviation of 0.58% compared to 0.55% and 1.94% respectively for single energy CT (SECT) and SPR measurement. Our ex vivo study indicates that the stoichiometric DECT SPR calibration method has the potential to be more accurate than SECT calibration under ideal conditions although beam hardening effects and other image artifacts may increase this uncertainty.