Concept: A randomised multicentre trial of first line chemotherapy comparing three weekly cabazitaxel versus weekly paclitaxel in HER2 negative metastatic breast cancer.

BACKGROUND: Paclitaxel is commonly used as first-line chemotherapy for HER2-negative metastatic breast cancer (MBC) patients. However, with response rates of 21.5-53.7% and significant risk of peripheral neuropathy, there is need for better chemotherapy. PATIENTS AND METHODS: This open-label phase II/III trial randomised HER2-negative MBC patients 1:1 to either 6 cycles of three-weekly cabazitaxel (25 mg/m2), or, weekly paclitaxel (80 mg/m2) over 18 weeks. The primary endpoint was progression free survival (PFS). Secondary endpoints included objective response rate (ORR), time to response (TTR), overall survival (OS), safety and tolerability and quality of life (QoL). RESULTS: 158 patients were recruited. Comparing cabazitaxel to paclitaxel, median PFS was 6.7 vs 5.8 months (HR 0.87; 80%CI 0.70-1.08, P = 0.4). There was no difference in median OS (20.6 vs 18.2 months, HR 1.00; 95%CI 0.69-1.45, P = 0.99), ORR (41.8% vs 36.7%) or TTR (HR 1.09; 95%CI 0.68-1.75, P = 0.7). Grade ≥3 adverse events occurred in 41.8% on cabazitaxel and 46.8% on paclitaxel; the most common being neutropenia (16.5%) and febrile neutropenia (12.7%) cabazitaxel and neutropenia (8.9%) and lung infection (7.6%) paclitaxel. Peripheral neuropathy of any grade occurred in 54.5% paclitaxel vs 16.5% cabazitaxel. Mean EQ-5D-5L single index utility score (+0.05; 95%CI 0.004-0.09, P = 0.03) and visual analogue scale score (+7.7; 95%CI 3.1-12.3, P = 0.001) were higher in cabazitaxel vs paclitaxel. CONCLUSIONS: Three-weekly cabazitaxel in HER2-negative MBC does not significantly improve PFS compared to weekly paclitaxel, although it has a lower risk of peripheral neuropathy with better patient reported QoL outcomes. It is well tolerated and requires fewer hospital visits.

Brain imaging of executive function with the computerised multiple elements test.

The Computerised Multiple Elements Test (CMET) is a novel executive task to assess goal management and maintenance suitable for use within the fMRI environment. Unlike classical executive paradigms, it resembles neuropsychological multi-elements tests that capture goal management in a more ecological way, by requiring the participant to switch between four simple games within a specified time period. The present study aims to evaluate an fMRI version of the CMET and examine its brain correlates. Thirty-one healthy participants performed the task during fMRI scanning. During each block, they were required to play four simple games, with the transition between games being made either voluntarily (executive condition) or automatically (control condition). The executive condition was associated with increased activity in fronto-parietal and cingulo-opercular regions, with anterior insula activity linked to better task performance. In an additional analysis, the activated regions showed to form functional networks during resting-state and to overlap the executive fronto-parietal and cingulo-opercular networks identified in resting-state with independently defined seeds. These results show the ability of the CMET to elicit activity in well-known executive networks, becoming a potential tool for the study of executive impairment in neurological and neuropsychiatric populations in a more ecological way than classical paradigms.

Health-related quality of life in men with metastatic castration-resistant prostate cancer.

Metastatic castration-resistant prostate cancer (MCRPC) is a chronic disease with several therapeutic options. By definition, all approaches to treatment are palliative in intent and improving health-related quality of life (HRQoL) is an important goal of therapy. Several tools exist for the assessment of HRQoL in MCRPC enabling cross-trial comparisons. In this article agents currently used in the management of MCRPC are reviewed from a HRQoL perspective.

Molecular pathology and clinical characteristics of oligodendroglial neoplasms.

To evaluate the role of molecular genetics in the routine clinic, we investigated allelic imbalance at 1p36, 19q13, 17p13, 10p12-15, and 10q22-26 and p53 mutation in 100 oligodendroglial neoplasms diagnosed at a single treatment center between 2000 and 2003. The -1p/-19q genotype, seen in 64, 34, 77, and 30% of OII, OAII, OIII, and OAIII respectively, was inversely related to p53 mutation and 17p13 loss. Genotype was unrelated to tumor location and could not distinguish high-grade tumors that presented de novo from those that progressed from a previous lower grade malignancy. Presentation with seizures was more common in cases with the -1p/-19q genotype, and these remained stable for longer before treatment. In longitudinal samples, 74% retained their initial histological differentiation, whereas 29% showed new genetic alterations, the -1p/-19q genotype being acquired in three cases. Loss of 1p36 and 19q13, 17p13, chromosome 10, and p53 mutation were significantly associated with survival from presentation in Kaplan-Meier analysis (p < 0.01), and loss of 1p36 and 19q13 and loss of 17p13 retained significance in multivariate analysis. In this recently diagnosed unselected series, clinical differences in tumors with and without the -1p/-19q genotype support a genetic approach to aid diagnosis and prognostication for oligodendroglial neoplasms.