Analytical model-based analysis of long-exposure images fromground-based telescopes

The search for Earth-like exoplanets requires high-contrast and high-angular resolution instruments, which designs can be very complex: they need an adaptive optics system to compensate for the effect of the atmospheric turbulence on image quality and a coronagraph to reduce the starlight and enable the companion imaging. During the instrument design phase and the error budget process, studies of performance as a function of optical errors are needed and require multiple end-to-end numerical simulations of wavefront errors through the optical system. In particular, the detailed analysis of long-exposure images enables to evaluate the image quality (photon noise level, impact of optical aberrations and of adaptive optics residuals, etc.). Nowadays simulating one long but finite exposure image means drawing several thousands of random frozen phase screens, simulating the image associated with each of them after propagation through the imaging instrument, and averaging all the images. Such a process is time consuming, demands a great deal of computer resources, and limits the number of parametric optimization. We propose an alternative and innovative method to directly express the statistics of ground-based images for long but finite exposure times. It is based on an analytical model, which only requires the statistical properties of the atmospheric turbulence. Such a method can be applied to optimize the design of future instruments such as SPHERE+ (VLT) or the planetary camera and spectrograph (PCS - ELT) or any ground-based instrument.Comment: 7 pages, 0 figur

Vandetanib for the Treatment of Metastatic Medullary Thyroid Cancer

Medullary thyroid cancer (MTC) represents an aggressive form of thyroid malignancy. Some may occur spontaneously or can be associated with Multiple Endocrine Neoplasia syndromes, or Familial Medullary Thyroid Cancer syndrome. In these patients, the protooncogene RET (rearranged during transfection) is mutated. In patients who have unresectable or metastatic disease, the long term prognosis is poor. New treatments for this disease have focused on the use of targeted agents that inhibit the receptor tyrosine kinase of RET. One of these treatments, Vandetanib (Caprelsa, Astra Zeneca), recently has received approval from the Food and Drug Administration for the treatment of patients with progressive locally advanced and/or metastatic disease. This review highlights the studies that led to the drug’s approval, and discusses on the potential financial costs of treatment and side effects of this therapy. The main clinical studies evaluating Vandetanib for the treatment of other solid tumors will also be reviewed

A Randomized, Double-Blind Noninferiority Study to Evaluate the Efficacy of the Cabozantinib Tablet at 60 mg Per Day Compared with the Cabozantinib Capsule at 140 mg Per Day in Patients with Progressive, Metastatic Medullary Thyroid Cancer

Cabozantinib; Medullary thyroid cancer; Tyrosine kinase inhibitorCabozantinib; Càncer medul·lar de tiroides; Inhibidor de la tirosina cinasaCabozantinib; Cáncer medular de tiroides; Inhibidor de la tirosina cinasaBackground: Cabozantinib inhibits pathways involved in medullary thyroid cancer (MTC). Cabozantinib is approved as 140 mg/day in capsules for MTC and 60 mg/day in tablets for other solid tumors. This study compared the two doses in progressive metastatic MTC. Methods: In this Phase 4, randomized, double-blind noninferiority (NI) trial (NCT01896479), patients with progressive metastatic MTC were randomized 1:1 to cabozantinib 60 mg/day tablet or 140 mg/day capsules. The primary end point was progression-free survival (PFS) by blinded independent radiology committee (BIRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. NI would be concluded if the upper 95% confidence interval [CI] for the PFS hazard ratio (HR) was less than the NI margin, 1.58. The secondary end point was objective response rate (ORR) by BIRC per RECIST v1.1; additional end points included safety and pharmacokinetics. Results: At data cutoff (July 15, 2020), 247 patients were randomized to the 60 mg/day tablet arm (n = 123) and the 140 mg/day capsules arm (n = 124). NI was not met (median PFS 11.0 months vs. 13.9 months in the 60 and 140 mg/day arms [HR 1.24; CI 0.90–1.70; p = 0.19]). The ORR was 33% in both arms. Generally, adverse event (AE) incidence was lower in the 60 mg/day arm (Grade 3/4, 63% vs. 72%), as were dose reductions (69% vs. 81%) and treatment discontinuations due to AEs (23% vs. 36%). Initially, cabozantinib plasma concentrations were higher in the 140 mg/day arm but became similar between arms at later time points. Conclusions: PFS NI of the cabozantinib 60 mg/day tablet vs. 140 mg/day capsules was not met. The 60 mg/day tablet had the same ORR and lower rates of AEs.This work was supported by Exelixis, Inc., Alameda, CA, USA (no grant number). Exelixis was involved in the study design, the collection, analysis, and interpretation of data, the writing of the report, and the decision to submit for publication

Use of lenvatinib in the treatment of radioiodine-refractory differentiated thyroid cancer: a multidisciplinary perspective for daily practice

Differentiated thyroid cancer; Lenvatinib; ToxicityCáncer diferenciado de tiroides; Lenvatinib; ToxicidadCàncer diferenciat de tiroide; Lenvatinib; ToxicitatBackground Most thyroid cancers of follicular origin have a favorable outcome. Only a small percentage of patients will develop metastatic disease, some of which will become radioiodine refractory (RAI-R). Important challenges to ensure the best therapeutic outcomes include proper, timely, and appropriate diagnosis; decisions on local, systemic treatments; management of side effects of therapies; and a good relationship between the specialist, patients, and caregivers. Methods With the aim of providing suggestions that can be useful in everyday practice, a multidisciplinary group of experts organized the following document, based on their shared clinical experience with patients with RAI-R differentiated thyroid cancer (DTC) undergoing treatment with lenvatinib. The main areas covered are patient selection, initiation of therapy, follow-up, and management of adverse events. Conclusions It is essential to provide guidance for the management of RAI-R DTC patients with systemic therapies, and especially lenvatinib, since compliance and adherence to treatment are fundamental to achieve the best outcomes. While the therapeutic landscape in RAI-R DTC is evolving, with new targeted therapies, immunotherapy, etc., lenvatinib is expected to remain a first-line treatment and mainstay of therapy for several years in the vast majority of patients and settings. The guidance herein covers baseline work-up and initiation of systemic therapy, relevance of symptoms, multidisciplinary assessment, and patient education. Practical information based on expert experience is also given for the starting dose of lenvatinib, follow-up and monitoring, as well as the management of adverse events and discontinuation and reinitiating of therapy. The importance of patient engagement is also stressed.Eisai Europe sponsored the expert panel and editorial assistance providing medical writing support. Eisai Europe had no editorial control over this manuscript and the views expressed are those of the authors. JC, DD, CD, SL, ML, RNM, KN, SS,GS, and LDL received an honorarium from Eisai Europe for time attending the panel and for editorial contribution to the present manuscript. Beate Bartès, as president of Association Vivre sans Thyroïde, received a donation from Eisai Europe. Kate Farnell received, on behalf of Butterfly Thyroid Cancer Trust, a donation from Eisai Europe

Kinase inhibitors for advanced medullary thyroid carcinoma

The recent availability of molecular targeted therapies leads to a reconsideration of the treatment strategy for patients with distant metastases from medullary thyroid carcinoma. In patients with progressive disease, treatment with kinase inhibitors should be offered

James Webb Space Telescope Optical Simulation Testbed I: Overview and First Results

The James Webb Space Telescope (JWST) Optical Simulation Testbed (JOST) is a tabletop workbench to study aspects of wavefront sensing and control for a segmented space telescope, including both commissioning and maintenance activities. JOST is complementary to existing optomechanical testbeds for JWST (e.g. the Ball Aerospace Testbed Telescope, TBT) given its compact scale and flexibility, ease of use, and colocation at the JWST Science & Operations Center. We have developed an optical design that reproduces the physics of JWST's three-mirror anastigmat using three aspheric lenses; it provides similar image quality as JWST (80% Strehl ratio) over a field equivalent to a NIRCam module, but at HeNe wavelength. A segmented deformable mirror stands in for the segmented primary mirror and allows control of the 18 segments in piston, tip, and tilt, while the secondary can be controlled in tip, tilt and x, y, z position. This will be sufficient to model many commissioning activities, to investigate field dependence and multiple field point sensing & control, to evaluate alternate sensing algorithms, and develop contingency plans. Testbed data will also be usable for cross-checking of the WFS&C Software Subsystem, and for staff training and development during JWST's five- to ten-year mission.Comment: Proceedings of the SPIE, 9143-150. 13 pages, 8 figure