Dataset Information

Revisiting Bevacizumab?+?Cytotoxics Scheduling Using Mathematical Modeling: Proof of Concept Study in Experimental Non-Small Cell Lung Carcinoma.

ABSTRACT: Concomitant administration of bevacizumab and pemetrexed-cisplatin is a common treatment for advanced nonsquamous non-small cell lung cancer (NSCLC). Vascular normalization following bevacizumab administration may transiently enhance drug delivery, suggesting improved efficacy with sequential administration. To investigate optimal scheduling, we conducted a study in NSCLC-bearing mice. First, experiments demonstrated improved efficacy when using sequential vs. concomitant scheduling of bevacizumab and chemotherapy. Combining this data with a mathematical model of tumor growth under therapy accounting for the normalization effect, we predicted an optimal delay of 2.8 days between bevacizumab and chemotherapy. This prediction was confirmed experimentally, with reduced tumor growth of 38% as compared to concomitant scheduling, and prolonged survival (74 vs. 70 days). Alternate sequencing of 8 days failed in achieving a similar increase in efficacy, thus emphasizing the utility of modeling support to identify optimal scheduling. The model could also be a useful tool in the clinic to personally tailor regimen sequences.

SUBMITTER: Imbs DC

PROVIDER: S-EPMC5784740 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Revisiting Bevacizumab + Cytotoxics Scheduling Using Mathematical Modeling: Proof of Concept Study in Experimental Non-Small Cell Lung Carcinoma.

Imbs Diane-Charlotte DC El Cheikh Raouf R Boyer Arnaud A Ciccolini Joseph J Mascaux Céline C Lacarelle Bruno B Barlesi Fabrice F Barbolosi Dominique D Benzekry Sébastien S

CPT: pharmacometrics & systems pharmacology 20171207 1

Concomitant administration of bevacizumab and pemetrexed-cisplatin is a common treatment for advanced nonsquamous non-small cell lung cancer (NSCLC). Vascular normalization following bevacizumab administration may transiently enhance drug delivery, suggesting improved efficacy with sequential administration. To investigate optimal scheduling, we conducted a study in NSCLC-bearing mice. First, experiments demonstrated improved efficacy when using sequential vs. concomitant scheduling of bevacizum ...[more]

PMID: 29218795

Similar Datasets

Project description:This paper concerns the feasibility of x-ray differential phase contrast (DPC) tomosynthesis imaging using a grating-based DPC benchtop experimental system, which is equipped with a commercial digital flat-panel detector and a medical-grade rotating-anode x-ray tube. An extensive system characterization was performed to quantify its imaging performance.The major components of the benchtop system include a diagnostic x-ray tube with a 1.0 mm nominal focal spot size, a flat-panel detector with 96 μm pixel pitch, a sample stage that rotates within a limited angular span of ± 30°, and a Talbot-Lau interferometer with three x-ray gratings. A total of 21 projection views acquired with 3° increments were used to reconstruct three sets of tomosynthetic image volumes, including the conventional absorption contrast tomosynthesis image volume (AC-tomo) reconstructed using the filtered-backprojection (FBP) algorithm with the ramp kernel, the phase contrast tomosynthesis image volume (PC-tomo) reconstructed using FBP with a Hilbert kernel, and the differential phase contrast tomosynthesis image volume (DPC-tomo) reconstructed using the shift-and-add algorithm. Three inhouse physical phantoms containing tissue-surrogate materials were used to characterize the signal linearity, the signal difference-to-noise ratio (SDNR), the three-dimensional noise power spectrum (3D NPS), and the through-plane artifact spread function (ASF).While DPC-tomo highlights edges and interfaces in the image object, PC-tomo removes the differential nature of the DPC projection data and its pixel values are linearly related to the decrement of the real part of the x-ray refractive index. The SDNR values of polyoxymethylene in water and polystyrene in oil are 1.5 and 1.0, respectively, in AC-tomo, and the values were improved to 3.0 and 2.0, respectively, in PC-tomo. PC-tomo and AC-tomo demonstrate equivalent ASF, but their noise characteristics quantified by the 3D NPS were found to be different due to the difference in the tomosynthesis image reconstruction algorithms.It is feasible to simultaneously generate x-ray differential phase contrast, phase contrast, and absorption contrast tomosynthesis images using a grating-based data acquisition setup. The method shows promise in improving the visibility of several low-density materials and therefore merits further investigation.

Dataset Information

Revisiting Bevacizumab?+?Cytotoxics Scheduling Using Mathematical Modeling: Proof of Concept Study in Experimental Non-Small Cell Lung Carcinoma.

Publications

Revisiting Bevacizumab + Cytotoxics Scheduling Using Mathematical Modeling: Proof of Concept Study in Experimental Non-Small Cell Lung Carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure