Patient-reported outcomes predict survival and adverse events following anticancer treatment initiation in advanced HER2-positive breast cancer.

BACKGROUND: The prognostic value of patient-reported outcomes (PROs) has been minimally explored in advanced breast cancer (BC), and their comparative prognostic performance against Eastern Cooperative Oncology Group performance status (ECOG PS) is largely unknown. PATIENTS AND METHODS: This study pooled individual participant data from clinical trials CLEOPATRA, EMILIA, and MARIANNE. Pre-treatment PRO associations with overall survival (OS), progression-free survival (PFS), and grade ≥3 adverse events were evaluated via Cox proportional hazards regression. Prognostic performance was assessed with the C-statistic (c). PRO values were collected via the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire. All analyses were stratified by study and treatment arms. Analyses adjusted for known prognostic variables were conducted. Exploratory analysis of the prognostic performance of PROs compared to ECOG PS was undertaken. RESULTS: The study included data from 2894 patients initiated on contemporary therapies including pertuzumab (n = 765), trastuzumab (n = 1173), trastuzumab emtansine (n = 1225), taxanes (n = 1173), lapatinib (n = 496), and capecitabine (n = 496). On univariable and adjusted analysis, patient-reported physical well-being, functional well-being, and BC subscale were all identified to be associated with OS, PFS, and grade ≥3 adverse events (P < 0.05). Patient-reported physical well-being was the most prognostic PRO for all assessed outcomes. The OS prognostic performance of physical well-being (c = 0.58) was superior to ECOG PS (c = 0.56) (P < 0.05), with multivariable analysis indicating that both provide independent information (P < 0.0001). CONCLUSIONS: PROs were identified as independent prognostic factors for OS, PFS, and grade ≥3 adverse events in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced BC initiating contemporary treatment options. Further, patient-reported physical well-being was more prognostic of OS than ECOG PS and contained independent information. PROs have value as prognostic and stratification factors for clinical use and research trials of anticancer treatment in HER2-positive ABC.

Ice sheet flow with thermally activated sliding. Part 1: the role of advection.

Flow organization into systems of fast-moving ice streams is a well-known feature of ice sheets. Fast motion is frequently the result of sliding at the base of the ice sheet. Here, we consider how this basal sliding is first initiated as the result of changes in bed temperature. We show that an abrupt sliding onset at the melting point, with no sliding possible below that temperature, leads to rapid drawdown of cold ice and refreezing as the result of the increased temperature gradient within the ice, and demonstrate that this result holds regardless of the mechanical model used to describe the flow of ice. Using this as a motivation, we then consider the possibility of a region of 'subtemperate sliding' in which sliding at reduced velocities occurs in a narrow range of temperatures just below the melting point. We confirm that this prevents the rapid drawdown of ice and refreezing of the bed, and construct a simple numerical method for computing steady-state ice sheet profiles that include a subtemperate region. The stability of such an ice sheet is analysed in a companion paper.

No parallel between the biochemical course of acute pancreatitis and morphologic findings.

The clinical, biochemical (serum enzymes), and morphologic course of acute pancreatitis was studied in 83 consecutive patients from time of admission until 3 months after discharge. At discharge, all 75 surviving patients had no more symptoms of acute pancreatitis, even though amylase (in 11%) and lipase (in 25%) were still elevated, computed tomography (CT) findings still abnormal (in 81%), and necrosis amounting up to 50% of the gland still present (in 24%). There was no significant correlation between serum enzymes and CT findings at discharge. Three months later, with the exception of one patient with an acute relapse of the disease, all followed-up patients were free of symptoms and had normal serum amylase, whereas lipase was still elevated in 10%, and CT findings abnormal in 23%. Subsiding symptoms provided a more accurate picture of the patients' recovery than the biochemical markers, and even more so that the morphologic findings.