Spectropolarimetric Study on Circumstellar Structure of Microquasar LS I +61deg 303

We present optical linear spectropolarimetry of the microquasar LS I +61$^{\circ}$ 303. The continuum emission is mildly polarized (up to 1.3 %) and shows almost no temporal change. We find a distinct change of polarization across the H$\alpha$ emission line, indicating the existence of polarization component intrinsic to the microquasar. We estimate the interstellar polarization (ISP) component from polarization of the H$\alpha$ line and derive the intrinsic polarization component. The wavelength dependence of the intrinsic component is well explained by Thomson scattering in equatorial disk of the Be-type mass donor. The position angle (PA) of the intrinsic polarization $\sim 25^{\circ}$ represents the rotational axis of the Be disk. This PA is nearly perpendicular to the PA of the radio jet found during quiescent phases. Assuming an orthogonal disk-jet geometry around the compact star, the rotational axis of the accretion disk is almost perpendicular to that of the Be disk. Moreover, according to the orbital parameters of the microquasar, the compact star is likely to get across the Be disk around their periastron passage. We discuss the peculiar circumstellar structure of this microquasar inferred from our observation and possible connection with its high-energy activities.Comment: 17pages, 7figures; accepted for Publications of the Astronomical Society of Japa

Trastuzumab Deruxtecan in HER2-Positive Metastatic Breast Cancer Patients with Brain Metastases: A DESTINY-Breast01 Subgroup Analysis

Trastuzumab deruxtecán; Cáncer de mama metastásico; Metástasis cerebralesTrastuzumab deruxtecan; Metastatic breast cancer; Brain metastasesTrastuzumab deruxtecan; Càncer de mama metastàtic; Metàstasis cerebralsDESTINY-Breast01 (NCT03248492) evaluated trastuzumab deruxtecan (T-DXd; DS-8201) in patients with heavily pretreated HER2-positive metastatic breast cancer (mBC). We present a subgroup of 24 patients with a history of treated brain metastases (BM), a population with limited treatment options. In patients with BMs, the confirmed objective response rate (cORR) was 58.3% [95% confidence interval (CI), 36.6%–77.9%], and the median progression-free survival (mPFS) was 18.1 months (95% CI, 6.7–18.1 months). In patients without BMs (n = 160), cORR was 61.3% and mPFS was 16.4 months. Eight patients (47.1%) experienced a best overall intracranial response of partial response or complete response. Seven patients (41.2%) had a best percentage change in brain lesion diameter from baseline consistent with stable disease. Two patients (8.3%) with BMs and two (1.3%) without BMs experienced progression in the brain. The safety profile of T-DXd was consistent with previous studies. The durable clinical activity of T-DXd in this population warrants further investigation. Significance: Advances in treating HER2-positive metastatic breast cancer have greatly improved patient outcomes, but intracranial progression remains an important risk for which few therapeutic options are currently available. T-DXd demonstrated durable efficacy in patients with stable, treated BMs.AstraZeneca (AstraZeneca PLC) i American Regent (American Regent, Inc.)

Adjuvant immunochemotherapy with protein-bound polysaccharide K for colon cancer in relation to oncogenic β-catenin activation

Division of Translational and Clinical Oncolog

Time course and management of key adverse events during the randomized phase III SOLAR-1 study of PI3K inhibitor alpelisib plus fulvestrant in patients with HR-positive advanced breast cancer.

Background Alpelisib (α-selective phosphatidylinositol 3-kinase inhibitor) plus fulvestrant is approved in multiple countries for men and postmenopausal women with PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer following progression on or after endocrine therapy. A detailed understanding of alpelisib's safety profile should inform adverse event (AE) management and enhance patient care. Patients and methods AEs in the phase III SOLAR-1 trial were assessed in patients with and without PIK3CA mutations. The impact of protocol-specified AE-management recommendations was evaluated, including an amendment to optimize hyperglycemia and rash management. Results Patients were randomly assigned to receive fulvestrant plus alpelisib (n = 284) or placebo (n = 287). The most common grade 3/4 AEs with alpelisib were hyperglycemia (grade 3, 32.7%; grade 4, 3.9%), rash (grade 3, 9.9%), and diarrhea (grade 3, 6.7%). Median time to onset of grade ≥3 toxicity was 15 days (hyperglycemia, based on fasting plasma glucose), 13 days (rash), and 139 days (diarrhea). Metformin alone or in combination with other antidiabetic agents was used by most patients (87.1%) with hyperglycemia. Preventive anti-rash medication resulted in lower incidence (any grade, 26.7% versus 64.1%) and severity of rash (grade 3, 11.6% versus 22.7%) versus no preventative medication. Discontinuations due to grade ≥3 AEs were lower following more-detailed AE management guidelines (7.9% versus 18.1% previously). Patients with PIK3CA mutations had a median alpelisib dose intensity of 248 mg/day. Median progression-free survival with alpelisib was 12.5 and 9.6 months for alpelisib dose intensities of ≥248 mg/day and Conclusions Hyperglycemia and rash occurred early during alpelisib treatment, while diarrhea occurred at a later time point. Early identification, prevention, and intervention, including concomitant medications and alpelisib dose modifications, resulted in less severe toxicities. Reductions in treatment discontinuations and improved progression-free survival at higher alpelisib dose intensities support the need for optimal AE management. ClinicalTrials.gov Id NCT02437318