Commissioning and validation of BrainLAB cones for 6X FFF and 10X FFF beams on a Varian TrueBeam STx.

Small field dosimetry is a challenging task. The difficulties of small field measurements, particularly stereotactic field size measurements, are highlighted by the large interinstitution variability that can be observed for circular cone collimator commissioning measurements. We believe the best way to improve the consistency of small field measurements is to clearly document and share the results of small field measurements. In this work we report on the commissioning and validation of a BrainLAB cone system for 6 MV and 10 MV flattening filter-free (FFF) beams on a Varian TrueBeam STx. Commissioning measurements consisted of output factors, percent depth dose, and off-axis factor measurements with a diode. Validation measurements were made in a polystyrene slab phantom at depths of 5 cm, 10 cm, and 15 cm using radiochromic film. Output factors for the 6xFFF cones are 0.689, 0.790, 0.830, 0.871, 0.890, and 0.901 for 4 mm, 6 mm, 7.5 mm, 10 mm, 12.5 mm, and the 15 mm cones, respectively. Output factors for the 10xFFF cones are 0.566, 0.699, 0.756, 0.826, 0.864, and 0.888 for 4 mm, 6 mm, 7.5 mm, 10 mm, 12.5 mm, and the 15 mm cones, respectively. The full width half maximum values of the off-axis factors agreed with the nominal cone size to within 0.5 mm. Validation measurements showed an agreement of absolute dose between calculation and plan of < 3.6%, and an agreement of field sizes of ≤ 0.3 mm in all cases. Radiochromic film validation measurements show reasonable agreement with beam models for circular collimators based on diode commissioning measurements.

Radiation-induced acid ceramidase confers prostate cancer resistance and tumor relapse.

Escape of prostate cancer (PCa) cells from ionizing radiation-induced (IR-induced) killing leads to disease progression and cancer relapse. The influence of sphingolipids, such as ceramide and its metabolite sphingosine 1-phosphate, on signal transduction pathways under cell stress is important to survival adaptation responses. In this study, we demonstrate that ceramide-deacylating enzyme acid ceramidase (AC) was preferentially upregulated in irradiated PCa cells. Radiation-induced AC gene transactivation by activator protein 1 (AP-1) binding on the proximal promoter was sensitive to inhibition of de novo ceramide biosynthesis, as demonstrated by promoter reporter and ChIP-qPCR analyses. Our data indicate that a protective feedback mechanism mitigates the apoptotic effect of IR-induced ceramide generation. We found that deregulation of c-Jun induced marked radiosensitization in vivo and in vitro, which was rescued by ectopic AC overexpression. AC overexpression in PCa clonogens that survived a fractionated 80-Gy IR course was associated with increased radioresistance and proliferation, suggesting a role for AC in radiotherapy failure and relapse. Immunohistochemical analysis of human PCa tissues revealed higher levels of AC after radiotherapy failure than those in therapy-naive PCa, prostatic intraepithelial neoplasia, or benign tissues. Addition of an AC inhibitor to an animal model of xenograft irradiation produced radiosensitization and prevention of relapse. These data indicate that AC is a potentially tractable target for adjuvant radiotherapy.