ABSTRACT
Purpose: SABR is a treatment option for patients with lung tumors that employs fiducials to track tumors during the breathing cycle. Currently, there is a paucity of data on how relative fiducial location and patient clinical characteristics affect fiducial tracking and clinical outcomes. This study aimed to identify factors that reduce the number of fiducials tracked with respiratory motion management during SABR. Methods and Materials: An institutional review board-approved retrospective review was performed of patients receiving robotic SABR for lung tumors at our institution from 2016 to 2019. Clinical data including demographics, medical history, treatment data, and follow-up were collected. Fiducial geometries were obtained with Velocity contouring software and MATLAB. Mann-Whitney U, χ2, and t tests were completed using MedCalc. Results: A total of 73 patients with 77 treatments were identified. The χ2 analysis revealed that chronic obstructive pulmonary disease was associated with having 3 or more fiducials tracked (P = .034). Tumors in lower lobes were associated with higher rates of uncertainty errors (P = .015). The number of fiducials tracked had no effect on local tumor control or overall survival, with a median of 36 months of follow-up. A total of 28 treatments had fiducial centroid data available for geometric analysis. The most common tracking errors were rigid body error (RBE; 57%) and spacing errors (36.4%). Spacing errors had a shorter average minimum interfiducial distance than nonspacing errors (1.0 cm vs 1.7 cm, respectively; P = .017). RBE treatments had a longer average maximum distance than non-RBE treatments (4.0 cm vs 3.0 cm; P = .022). Conclusions: Greater motion in lower lobes can contribute to certain tracking errors that prevent more fiducials from being tracked. Maintaining interfiducial distance between experimentally determined guidelines may limit spacing errors and RBEs, the 2 most common tracking errors. An increased number of patients in a data set may result in stronger correlations between patient and tumor factors and outcomes.
ABSTRACT
Lipoxygenases (LOXs) catalyze the oxidation of polyunsaturated fatty acids and synthesize oxylipin products that drive important cellular signaling processes in plants and animals. While there has been indirect evidence presented for the interaction of mammalian LOXs with membranes, a quantitative study of the molecular details of LOX-membrane interactions is lacking. Here, we mimicked biological membranes using surface plasmon resonance (SPR) sensor chips derivatized with 2-D planar lipophilic anchors (2D LP) to capture liposomes of varying phospholipid compositions that self-assemble into lipid bilayers on the SPR chip. The sensor chip surfaces were then used to investigate the membrane-binding properties of model LOX enzymes. SPR binding assays displayed reproducible and stable liposome capture to the sensor chip surface that allowed for the detailed characterization of LOX-membrane interactions. Our studies demonstrate a calcium-dependence for the membrane binding activities of coral 8R-LOX and human 15-LOX-2. Furthermore, our data confirm the importance of key membrane insertion loop residues in each of these LOX enzymes for membrane binding activity. Experiments utilizing model plant and human LOXs reveal differences in membrane-binding specificities. Our study establishes and validates a robust SPR-based platform using 2D LP sensor chips that allows for the detailed study of LOX-membrane interactions under different experimental conditions, including altered membrane compositions. Collectively, this investigation improves our overall understanding of LOX-membrane interaction properties, and our SPR-based approach holds potential for future use in the development of LOX-based therapeutics.
