Inflammation markers and cognitive performance in breast cancer survivors 20 years after completion of chemotherapy: a cohort study

BACKGROUND: Inflammation is an important candidate mechanism underlying cancer and cancer treatment-related cognitive impairment. We investigated levels of blood cell-based inflammatory markers in breast cancer survivors on average 20 years after chemotherapy and explored the relation between these markers and global cognitive performance. METHODS: One hundred sixty-six breast cancer survivors who received post-surgical radiotherapy and six cycles of adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy on average 20 years before enrollment were compared with 1344 cancer-free women from a population-based sample (50-80 years old). Breast cancer survivors were excluded if they used adjuvant hormonal therapy or if they developed relapse, metastasis, or second primary malignancies. Systemic inflammation status was assessed by the granulocyte-to-lymphocyte ratio (GLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). Cognitive performance was assessed using an extensive neuropsychological test battery from which the general cognitive factor was derived to evaluate global cognitive performance. We examined the association between cancer, the general cognitive factor, and inflammatory markers using linear regression models. RESULTS: Breast cancer survivors had a lower general cognitive factor than non-exposed participants from the comparator group (mean difference = -0.21; 95% confidence interval (CI) -0.35 to -0.06). Inflammatory markers were higher in cancer survivors compared with non-exposed participants (mean difference for log(GLR) = 0.31; 95% CI 0.24 to 0.37, log(PLR) = 0.14; 95% CI 0.09 to 0.19, log(SII) = 0.31; 95% CI 0.24 to 0.39). The association between higher levels of inflammatory markers and lower general cognitive factor was statistically significant in cancer survivors but not among non-exposed participants. We found a group-by-inflammatory marker interaction; cancer survivors showed additional lower general cognitive factor per standard deviation increase in inflammatory markers (P for interaction for GLR = 0.038, PLR = 0.003, and SII = 0.033). CONCLUSIONS: This is the first study to show that (1) cancer survivors have increased levels of inflammation on average 20 years after treatment and (2) these inflammatory levels are associated with lower cognitive performance. Although this association needs verification by a prospective study to determine causality, our findings can stimulate research on the role of inflammation in long-term cognitive problems and possibilities to diminish such problems

Neurocognition in adults with intracranial tumors:Does location really matter?

OBJECTIVE: As preservation of cognitive functioning increasingly becomes important in the light of ameliorated survival after intracranial tumor treatments, identification of eloquent brain areas would enable optimization of these treatments. METHODS: This cohort study enrolled adult intracranial tumor patients who received neuropsychological assessments pre-irradiation, estimating processing speed, verbal fluency and memory. Anatomical magnetic resonance imaging scans were used for multivariate voxel-wise lesion-symptom predictions of the test scores (corrected for age, gender, educational level, histological subtype, surgery, and tumor volume). Potential effects of histological and molecular subtype and corresponding WHO grades on the risk of cognitive impairment were investigated using Chi square tests. P-values were adjusted for multiple comparisons (p < .001 and p < .05 for voxel- and cluster-level, resp.). RESULTS: A cohort of 179 intracranial tumor patients was included [aged 19-85 years, median age (SD) = 58.46 (14.62), 50% females]. In this cohort, test-specific impairment was detected in 20-30% of patients. Higher WHO grade was associated with lower processing speed, cognitive flexibility and delayed memory in gliomas, while no acute surgery-effects were found. No grading, nor surgery effects were found in meningiomas. The voxel-wise analyses showed that tumor locations in left temporal areas and right temporo-parietal areas were related to verbal memory and processing speed, respectively. INTERPRETATION: Patients with intracranial tumors affecting the left temporal areas and right temporo-parietal areas might specifically be vulnerable for lower verbal memory and processing speed. These specific patients at-risk might benefit from early-stage interventions. Furthermore, based on future validation studies, imaging-informed surgical and radiotherapy planning could further be improved

INTEGRATED DESIGN OF A LIGHTWEIGHT POSITIONING SYSTEM

Abstract In this paper a new approach to the design of positioning systems is introduced. The approach aims at the design of fast and accurate systems that are lightweight compared to classical designs. The new design reduces peak power requirements and thermal effects that deteriorate performance of the whole system

The EPTN consensus-based atlas for CT- and MR-based contouring in neuro-oncology

Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Posterior circulation ischaemia

One fifth of all transient ischaemic attacks (TIAs) and ischaemic strokes affect the posterior circulation. Patients with posterior circulation ischaemia can present with focal neurological symptoms (e.g., hemiparesis or visual field defects), but often also complain about accompanying non-focal neurological symptoms (e.g., non-rotatory dizziness). The prevalence and prognosis of non-focal neurological symptoms in these patients are largely unknown. In about a quarter of patients with posterior circulation ischaemia an atherosclerotic stenosis of the vertebral or basilar artery is found. The risk of recurrent stroke is much higher in these patients than in patients without a stenosis. Therefore, stenting of a symptomatic vertebrobasilar stenosis is often considered an attractive therapeutic option and this is widely performed despite the lack of evidence on the benefit and safety. This thesis focusses on the epidemiology of vertebrobasilar stenosis, the clinical presentation of patients with posterior circulation ischaemia, the prevalence and prognosis of non-focal neurological symptoms, and, finally, on the effects of stenting of symptomatic vertebral artery stenosis. We found a vertebral artery origin stenosis in almost 8% of patients with clinically manifest arterial disease but without recent vertebrobasilar ischaemia. Patients with such an asymptomatic vertebral artery origin stenosis had a low absolute risk of posterior circulation stroke during the following years (annual stroke rate, 0.4%). Almost three quarters of patients with a TIA or ischaemic stroke in the posterior circulation presented with both focal and non-focal neurological symptoms. Patients with non-focal neurological symptoms had no increased risk of cardiac events or death during long-term follow-up. The final part of this thesis reports the results of the Vertebral Artery Stenting Trial (VAST), a randomised phase II trial investigating the safety and feasibility of stenting in patients with recently symptomatic vertebral artery stenosis ≥50%. Patients were randomised to stenting and best medical treatment or to best medical treatment alone. The primary outcome, the composite of vascular death, stroke, or myocardial infarction within 30 days, occurred in 3 (5%; 95% CI, 0-11%) patients assigned to stenting and in 1 (2%; 95% CI, 0-5%) patient assigned to medical treatment. In both groups the cumulative incidences of posterior circulation stroke during a median follow-up of three years were low: 12% (95% CI, 6-24%) in the stenting group and 7% (95% CI, 2-17%) in the medical treatment group. We conclude that stenting of symptomatic vertebral artery stenosis is associated with a periprocedural risk of major vascular complications of about 5%. Because of the low risk of recurrent stroke in the medical treatment group during follow-up,stenting should not be considered a first-line treatment in current clinical practice. A phase III trial to assess the efficacy of stenting of symptomatic vertebral artery stenosis seems not feasible due to the low rates of posterior circulation stroke in VAST. Our findings contribute to the knowledge of symptoms and treatment of patients with posterior circulation ischaemia and vertebral artery stenosis. These findings are important for the development of preventive and treatment strategies for patients with posterior circulation ischaemia