Tolerability and Preliminary Outcomes of Adjuvant T-DM1 in HER2-Positive Breast Cancer After Neoadjuvant Therapy: The ATD Study.

Background/objectives: HER2-positive breast cancer (HER2BC) is an aggressive subtype, with neoadjuvant treatment (NAT) aiming to achieve a pathological complete response (pCR) to improve long-term outcomes. Trastuzumab emtansine (T-DM1) has been established as the standard of care in the adjuvant setting for HER2BC patients who do not obtain pCR. The ATD study aimed to evaluate the real-world tolerability of T-DM1 in this setting.

Adolescent maturation of dorsolateral prefrontal cortex glutamate:GABA and cognitive function is supported by dopamine-related neurobiology.

Developmental changes in prefrontal cortex (PFC) excitatory (glutamatergic, Glu) and inhibitory (gamma- aminobutryic acid, GABA) neurotransmitter balance (E:I) have been identified during human adolescence, potentially reflecting a critical period of plasticity that supports the maturation of PFC-dependent cognition. Animal models implicate increases in dopamine (DA) in regulating changes in PFC E:I during critical periods of development, however, mechanistic relationships between DA and E:I have not been studied in humans. Here, we used high field (7T) echo planar imaging (EPI) in combination with Magnetic Resonance Spectroscopic Imaging (MRSI) to assess the role of basal ganglia tissue iron-reflecting DA neurophysiology-in longitudinal trajectories of dorsolateral PFC Glu, GABA, and their relative levels (Glu:GABA) and working memory performance from adolescence to adulthood in 153 participants (ages 10-32 years old, 1-3 visits, 272 visits total).

Prefrontal excitation/inhibition balance supports adolescent enhancements in circuit signal to noise ratio.

The development and refinement of neuronal circuitry allow for stabilized and efficient neural recruitment, supporting adult-like behavioral performance. During adolescence, the maturation of PFC is proposed to be a critical period (CP) for executive function, driven by a break in balance between glutamatergic excitation and GABAergic inhibition (E/I) neurotransmission. During CPs, cortical circuitry fine-tunes to improve information processing and reliable responses to stimuli, shifting from spontaneous to evoked activity, enhancing the SNR, and promoting neural synchronization.

Apalutamide in Metastatic Castration-sensitive Prostate Cancer: Results from the Multicenter Real-world ARON-3 Study.

Background And Objective: Apalutamide (APA) is a treatment for metastatic castration-sensitive prostate cancer (mCSPC). In the ARON-3 study we investigated real-world experiences with APA treatment for mCSPC.

Methods: We retrospectively assessed real-world clinical outcomes for patients with mCSPC treated with APA in the ARON-3 study.

Efficacy and safety of prostate radiotherapy in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design.

Background: The 2 × 2 PEACE-1 study showed that combining androgen-deprivation therapy with docetaxel and abiraterone improved overall and radiographic progression-free survival in patients with de novo metastatic castration-sensitive prostate cancer. We aimed to examine the efficacy and safety of adding radiotherapy in this population.

Methods: We conducted an open-label, randomised, controlled, phase 3 trial with a 2 × 2 factorial design (PEACE-1) at 77 hospitals across Europe.