Search

At present, there exists few openly available methods for evaluation of simultaneous segmentation and registration algorithms. These methods allow for a combination of both techniques to track the tumor in complex settings such as adaptive radiotherapy. We have produced a quality assurance platform for evaluating this specific subset of algorithms using a preserved porcine lung in such that it is multi-modality compatible: positron emission tomography (PET), computer tomography (CT) and magnetic resonance imaging (MRI). A computer controlled respirator was constructed to pneumatically manipulate the lungs in order to replicate human breathing traces. A registration ground truth was provided using an in-house bifurcation tracking pipeline. Segmentation ground truth was provided by synthetic multi-compartment lesions to simulate biologically active tumor, background tissue and a necrotic core. The bifurcation tracking pipeline results were compared to digital deformations and used to evaluate three registration algorithms, Diffeomorphic demons, fast-symmetric forces demons and MiMVista's deformable registration tool. Three segmentation algorithms the Chan Vese level sets method, a Hybrid technique and the multi-valued level sets algorithm. The respirator was able to replicate three seperate breathing traces with a mean accuracy of 2-2.2%. Bifurcation tracking error was found to be sub-voxel when using human CT data for displacements up to 6.5 cm and approximately 1.5 voxel widths for displacements up to 3.5 cm for the porcine lungs. For the fast-symmetric, diffeomorphic and MiMvista registration algorithms, mean geometric errors were found to be [Formula: see text], [Formula: see text] and [Formula: see text] voxels widths respectively using the vector field differences and [Formula: see text], [Formula: see text] and [Formula: see text] voxel widths using the bifurcation tracking pipeline. The proposed phantom was found sufficient for accurate evaluation of registration and segmentation algorithms. The use of automatically generated anatomical landmarks proposed can eliminate the time and potential innacuracy of manual landmark selection using expert observers.

Purpose To determine the maximally tolerated dose (MTD) and pharmacokinetics of carboplatin plus KOS-862 (Epothilone D) a novel cytotoxic macrolide capable of causing mitotic arrest, in patients with advanced solid malignancies. Experimental Design Patients who have progressed on standard regimens were treated at four different levels of KOS-862(mg/m2)/Carboplatin(AUC): 50/5,75/5, 75/6 and 100/6 in a “3 + 3” phase I study study design to determine MTD. Patients received KOS-862 on Days 1 and 8, and carboplatin on day 1, of 3-week cycles. Pharmacokinetics of KOS-862 and Carboplatin were studied. Results Twenty-seven patients enrolled in the study. At the top dose level, 2 out of the 9 patients experienced Dose Limiting Toxicity. (grade 3 peripheral motor neuropathy in both patients) Twenty-seven patients had sufficient plasma data points for pharmacokinetic analysis Both the parent drug, KOS-862, and the major inactive metabolite Seco-D KOS-862 (KOS-1965) were quantified in plasma. Kinetics of KOS-862 were the same as seen in monotherapy studies using the same route and time of administration. Two patients had tumor response after study treatment. Ten of 20 evaluable patients had stable disease after 2 cycles of study treatment. The MTD in the present study was KOS-862 100 mg/m2 + carboplatin AUC = 6. Conclusions The pharmacokinetics of KOS-862 were similar in this combination study to those seen in previous monotherapy studies using the same route and time of administration. We have described the MTD of this schedule. The neurotoxicity seen with this regimen should be considered prior to its administration in unselected populations.