ABSTRACT
Introduction: Stereotactic body radiotherapy (SBRT) is a treatment option for spine metastases. The International Spine Radiosurgery Consortium (ISRC) has published consensus guidelines for target delineation in spine SBRT. A new software called Elements™ Spine SRS by Brainlab® that includes the module Elements SmartBrush Spine (v3.0, Munich, Germany) has been developed specifically for SBRT treatment of spine metastases, and the latter provides the ability to perform semiautomatic clinical target volume (CTV) generation based on gross tumor volume (GTV) localization and guidelines. The aims of our study were to evaluate this software by studying differences in volumes between semiautomatic CTV contours compared to manual contouring performed by an expert radiation oncologist and to determine the dosimetric impact of these differences on treatment plans. Methods: A total of 35 volumes ("Expert GTV" and "Expert CTV") from 30 patients were defined by a single expert. A semiautomatic definition of these 35 CTVs based on the location of "Expert GTV" and following ISRC guidelines was also performed in Elements SmartBrush Spine ("Brainlab CTV"). The spatial overlap between "Brainlab" and "Expert" CTVs was calculated using the Dice similarity coefficient (DSC). We considered a threshold of 0.80 or above to indicate that Elements SmartBrush Spine performed very well with adequate contours for clinical use. Two dosimetric treatment plans, each corresponding to a specific planning target volume (PTV; Expert PTV, Brainlab PTV), were created for 11 patients. Results: We showed that "Brainlab CTV" and "Expert CTV" mean volumes were 29.8 ± 16.1 and 28.7 ± 15.7 cm3, respectively (p = 0.23). We also showed that the mean DSC for semiautomatic contouring relative to expert manual contouring was 0.85 ± 0.08 and less than 0.80 in five cases. For metastases involving the vertebral body only (n = 13,37%), the mean DSC was 0.90 ± 0.03, and for ones involving other or several vertebral regions (n = 22.63%), the mean DSC was 0.81 ± 0.08 (p < 0.001). The comparison of dosimetric treatment plans was performed for equivalent PTV coverage. There were no differences between doses received by organs at risk (spinal cord and esophagus) for Expert and Brainlab PTVs, respectively. Conclusion: The results showed that the semiautomatic method had quite good accuracy and can be used in clinical routine even for complex lesions.
ABSTRACT
BACKGROUND: The public health threats imposed by toxoplasmosis worldwide and by malaria in sub-Saharan countries are directly associated with the capacity of their related causative agents Toxoplasma and Plasmodium, respectively, to colonize and expand inside host cells. Therefore, deciphering how these two Apicomplexan protozoan parasites access their host cells has been highlighted as a priority research with the perspective of designing anti-invasive molecules to prevent diseases. Central to the mechanism of invasion for both genera is mechanical force, which is thought to be applied by the parasite at the interface between the two cells following assembly of a unique cell-cell junction but this model lacks direct evidence and has been challenged by recent genetic studies. In this work, using parasites expressing the fluorescent core component of this junction, we analyze characteristic features of the kinematics of penetration of more than 1,000 invasion events. RESULTS: The majority of invasion events occur with a typical forward rotational progression of the parasite through a static junction into an invaginating host cell plasma membrane. However, if parasites encounter resistance and if the junction is not strongly anchored to the host cell cortex, as when parasites do not secrete the toxofilin protein and, therefore, are unable to locally remodel the cortical actin cytoskeleton, the junction travels retrogradely with the host cell membrane along the parasite surface allowing the formation of a functional vacuole. Kinetic measurements of the invasive trajectories strongly support a similar parasite driven force in both static and capped junctions, both of which lead to successful invasion. However, about 20% of toxofilin mutants fail to enter and eventually disengage from the host cell membrane while the secreted RhOptry Neck (RON2) molecules are posteriorally capped before being cleaved and released in the medium. By contrast in cells characterized by low cortex tension and high cortical actin dynamics junction capping and entry failure are drastically reduced. CONCLUSIONS: This kinematic analysis newly highlights that to invade cells parasites need to engage their motor with the junction molecular complex where force is efficiently applied only upon proper anchorage to the host cell membrane and cortex.
