Optimizing treatment management of trastuzumab deruxtecan in clinical practice of breast cancer.

INTRODUCTION: The antibody-drug conjugate trastuzumab deruxtecan (T-DXd) targets human epidermal growth factor receptor 2 (HER2) and has been evaluated in patients with HER2-positive unresectable/metastatic breast cancer in the phase II DESTINY-Breast01 trial (NCT03248492; DS8201-A-U201) and the randomized phase III DESTINY-Breast03 trial (NCT03529110; DS8201-A-U302). Approximately 20 additional studies are ongoing in breast cancer, including HER2-low breast cancer, and other solid tumor types within the DESTINY trial program. T-DXd has demonstrated a generally manageable safety profile, with low-grade hematologic and gastrointestinal adverse events (AEs) among the most common; interstitial lung disease (ILD)/pneumonitis has been observed in patients receiving T-DXd and can be severe. This review discusses the management of common AEs and AEs of special interest in patients with HER2-positive unresectable/metastatic breast cancer, including nausea and vomiting, neutropenia, infusion-related reactions, alopecia, fatigue, ILD/pneumonitis, and left ventricular dysfunction. METHODS: Expert opinions, institutional protocols, and strategies to help optimize AE management and maximize the potential benefits of T-DXd in patients with breast cancer from five oncologists treating patients with T-DXd in North America and Europe are discussed. RESULTS: Prophylaxis for nausea and vomiting and proactive management of ILD/pneumonitis are especially important in treating patients with T-DXd. Management strategies for other T-DXd-related AEs of interest (e.g. neutropenia, infusion-related reactions, alopecia, fatigue, and left ventricular dysfunction) are also discussed. CONCLUSIONS: This review provides context for understanding the usage, monitoring, and management practices of other health care providers and institutions with experience using T-DXd to help with safe and effective management of T-DXd-related AEs, particularly since the duration of T-DXd treatment may be quite long. Proper management of T-DXd-related AEs will allow optimal exposure and benefit from T-DXd and will help avoid premature discontinuation or improper dose reductions.

Implementing changes to a residency program curriculum before competency-based medical education: a survey of Canadian medical oncology program directors.

Background: Postgraduate medical education is undergoing a paradigm shift in many universities worldwide, transitioning from a time-based model to competency-based medical education (cbme). Residency programs might have to alter clinical rotations, educational curricula, assessment methods, and faculty involvement in preparation for cbme, a process not yet characterized in the literature. Methods: We surveyed Canadian medical oncology program directors on planned or newly implemented residency program changes in preparation for cbme. Results: Prior to implementing cbme, all program directors changed at least 1 clinical rotation, most commonly making hematology/oncology (74%) entirely outpatient and eliminating radiation oncology (64%). Introductory rotations were altered to focus on common tumour sites, and later rotations were changed to increase learner autonomy. Most program directors planned to enhance resident learning with electronic teaching modules (79%), new training experiences (71%), and academic half-day changes (50%). Most program directors (64%) planned to change assessment methods to be entirely based on entrustable professional activities. All programs had developed a competence committee to review learner progress, and most (86%) had integrated academic coaches. Conclusions: Transitioning to cbme led to major structural and curricular changes within medical oncology training programs. Identifying these commonly implemented changes could help other programs transition to cbme.

Broadband, millimeter-wave antireflection coatings for large-format, cryogenic aluminum oxide optics.

We present two prescriptions for broadband ($ {\sim} 77 - 252\;{\rm GHz} $), millimeter-wave antireflection coatings for cryogenic, sintered polycrystalline aluminum oxide optics: one for large-format (700 mm diameter) planar and plano-convex elements, the other for densely packed arrays of quasi-optical elements-in our case, 5 mm diameter half-spheres (called "lenslets"). The coatings comprise three layers of commercially available, polytetrafluoroethylene-based, dielectric sheet material. The lenslet coating is molded to fit the 150 mm diameter arrays directly, while the large-diameter lenses are coated using a tiled approach. We review the fabrication processes for both prescriptions, then discuss laboratory measurements of their transmittance and reflectance. In addition, we present the inferred refractive indices and loss tangents for the coating materials and the aluminum oxide substrate. We find that at 150 GHz and 300 K the large-format coating sample achieves $ (97 \pm 2)\% $ transmittance, and the lenslet coating sample achieves $ (94 \pm 3)\% $ transmittance.

Detection of B-mode polarization in the cosmic microwave background with data from the South Pole Telescope.

Gravitational lensing of the cosmic microwave background generates a curl pattern in the observed polarization. This "B-mode" signal provides a measure of the projected mass distribution over the entire observable Universe and also acts as a contaminant for the measurement of primordial gravity-wave signals. In this Letter we present the first detection of gravitational lensing B modes, using first-season data from the polarization-sensitive receiver on the South Pole Telescope (SPTpol). We construct a template for the lensing B-mode signal by combining E-mode polarization measured by SPTpol with estimates of the lensing potential from a Herschel-SPIRE map of the cosmic infrared background. We compare this template to the B modes measured directly by SPTpol, finding a nonzero correlation at 7.7σ significance. The correlation has an amplitude and scale dependence consistent with theoretical expectations, is robust with respect to analysis choices, and constitutes the first measurement of a powerful cosmological observable.