Advances in the Treatment of Primary Brain Tumors: The Realm of Immunotherapy

Central nervous system (CNS) tumors, although rare, represent a group of neoplasms that have a disproportionate morbidity and mortality. Despite advances in our understanding of tumor pathogenesis coupled with improvements in therapeutic options, overall survival for primary brain tumors remains dismal. Although challenging, newer approaches such as brachytherapy, immunotherapy, and electric field generators are currently being evaluated in the clinical setting with promising results. The field of immunotherapy in neurooncology is still in its infancy, but several advances have already been made, including the development of tumor vaccines, utilization of immune checkpoint inhibitors, and activation of tumor dendritic cells to stimulate the host’s immune system. Recent advances in noninvasive electric fields have been applied to the treatment of glioblastoma multiforme (GBM) with encouraging clinical outcome. In this chapter, we will review the latest advances in the treatment of glioblastoma multiforme with a focus on immunotherapy

Innovations in Metastatic Brain Tumor Treatment

Metastatic brain tumors (MBTs) are the most common intracranial tumor and occur in up to 40% of patients with certain cancer diagnoses. The most common and frequent primary locations are cancers originating from the lung, breast, kidney, gastrointestinal tract or skin, and also may arising from any part of the body. Treatment for brain metastasis management includes surgery, whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), and chemotherapy. Standard treatment for MBTs includes surgery and SRS which offer the best outcomes, while the WBRT is still an important treatment option for patients who cannot tolerate surgery and SRS or patients with multiple brain metastases. Newer approaches such as immunotherapy and molecularly targeted therapy (e.g., small molecules and monoclonal antibodies) are currently being evaluated for the treatment of MBTs. In this chapter, we will review current available treatments for MBTs and discuss treatments that are undergoing active investigation

Associations between smoking and caffeine consumption in two European cohorts

AIMS: To estimate associations between smoking initiation, smoking persistence and smoking heaviness and caffeine consumption in two population‐based samples from the Netherlands and the United Kingdom. DESIGN: Observational study employing data on self‐reported smoking behaviour and caffeine consumption. SETTING: Adults from the general population in the Netherlands and the United Kingdom. PARTICIPANTS: Participants from the Netherlands Twin Register [NTR: n = 21 939, mean age 40.8, standard deviation (SD) = 16.9, 62.6% female] and the Avon Longitudinal Study of Parents and Children (ALSPAC: n = 9086, mean age 33.2, SD = 4.7, 100% female). MEASUREMENTS: Smoking initiation (ever versus never smoking), smoking persistence (current versus former smoking), smoking heaviness (number of cigarettes smoked) and caffeine consumption in mg per day through coffee, tea, cola and energy drinks. FINDINGS: After correction for age, gender (NTR), education and social class (ALSPAC), smoking initiation was associated with consuming on average 52.8 [95% confidence interval (CI) = 45.6–60.0; NTR] and 59.5 (95% CI = 51.8–67.2; ALSPAC) mg more caffeine per day. Smoking persistence was also associated with consuming more caffeine [+57.9 (95% CI = 45.2–70.5) and +83.2 (95% CI = 70.2–96.3) mg, respectively]. Each additional cigarette smoked per day was associated with 3.7 (95% CI = 1.9–5.5; NTR) and 8.4 (95% CI = 6.9–10.0; ALSPAC) mg higher daily caffeine consumption in current smokers. Smoking was associated positively with coffee consumption and less strongly with cola and energy drinks. For tea, associations were positive in ALSPAC and negative in NTR. CONCLUSIONS: There appears to be a positive association between smoking and caffeine consumption in the Netherlands and the United Kingdom

Salivary cortisol in longitudinal associations between affective symptoms and midlife cognitive function: A British birth cohort study

Affective disorders are associated with accelerated cognitive ageing. However, current understanding of biological mechanisms which underlie these observed associations is limited. The aim of this study was to test: 1) Whether cortisol acts as a pathway in the association between depressive or anxiety symptoms across adulthood and midlife cognitive function; 2) Whether cortisol is associated with later depressive or anxiety symptoms, and cognitive function. Data were used from the National Child Development Study, a sample of infants born in mainland UK during one week of 1958. A measure of the accumulation of affective symptoms was derived from data collected from age 23 to 42 using the Malaise Inventory Scale. Salivary cortisol measures were available at age 44–45. Cognitive function (memory, fluency, information processing) and affective symptoms were assessed at the age of 50. Path models were run to test whether salivary cortisol explained the longitudinal association between depressive or anxiety disorder symptoms and cognitive function. Direct effects of affective symptoms are shown across early to middle adulthood on cognitive function in midlife (memory and information processing errors). However, there were no effects of affective symptoms on cognitive function through cortisol measures. Additionally, cortisol measures were not significantly associated with subsequent affective symptoms or cognitive function at the age of 50. These results do not provide clear evidence to suggest that cortisol plays a role in the association between affective symptoms and cognitive function over this period of time. These findings contribute to our understanding of how the association between affective symptoms and cognitive function operates over time

Associations between psychological intervention for anxiety disorders and risk of dementia: a prospective cohort study using national health-care records data in England

BACKGROUND: Meta-analyses support an association between anxiety in older adulthood and dementia. The aim of this study was to use routinely collected health data to test whether treatment of anxiety disorders through psychological intervention is associated with a lower incidence of dementia. METHODS: In this prospective cohort study, data from nationally provided psychological therapy services in England termed Improving Access to Psychological Therapies from 2012 to 2019 were linked to medical records, including dementia diagnoses as defined by the tenth edition of the International Classification of Diseases, up to 8 follow-up years later. Inclusion criteria were as follows: (1) patients who were aged 65 years and older; (2) patients with a probable anxiety disorder; and (3) those with no previous or current diagnosis of dementia. Cox proportional hazards models were constructed to test whether reliable improvement in anxiety following psychological intervention was associated with future dementia incidence. The primary outcome was all-cause dementia and cases were identified using ICD-10 dementia codes from Hospital Episode Statistics, Mental Health Services Dataset, and mortality data. For main analyses, hazards ratios (HRs) are presented. FINDINGS: Data from 128 077 people aged 65 years and older attending a nationally provided psychological intervention service in England were linked to medical records. 88 019 (69·0%) of 127 064 participants with available gender data were women and 39 585 (31·0%) were men. 111 225 (95·9%) of 115 989 with available ethnicity data were of White ethnicity. The mean age of the sample was 71·55 years (SD 5·69). Fully adjusted models included data from 111 958 people after 16 119 were excluded due to missing data on key variables or covariates. 4510 (4·0%) of 111 958 participants had a dementia diagnosis. The remaining 107 448 (96·0%) were censored either at date of death or when the final follow-up period available for analyses was reached. People who showed reliable improvement in anxiety had lower rates of later dementia diagnosis (3·9%) than those who did not show reliable improvement (5·1%). Reliable improvement in anxiety following psychological intervention was associated with reduced incidence of all-cause dementia (HR 0·83 [95% CI 0·78-0·88]), Alzheimer's disease (HR 0·85 [0·77-0·94]), and vascular dementia (HR 0·80 [0·71-0·90]). Effects did not differ depending on anxiety disorder diagnosis. INTERPRETATION: Results showed that reliable improvement in anxiety from psychological therapy was associated with reduced incidence of future dementia. There are multiple plausible explanations for this finding and further research is needed to distinguish between these possibilities. Missing data in the sample limit reliability of findings. FUNDING: Alzheimer's Society, Medical Research Council, Wellcome Trust, and UCLH National Institute for Health and Care Research Biomedical Research Centre

Associations between psychological therapy outcomes for depression and incidence of dementia

BACKGROUND: Depression is an important, potentially modifiable dementia risk factor. However, it is not known whether effective treatment of depression through psychological therapies is associated with reduced dementia incidence. The aim of this study was to investigate associations between reduction in depressive symptoms following psychological therapy and the subsequent incidence of dementia. METHODS: National psychological therapy data were linked with hospital records of dementia diagnosis for 119808 people aged 65+. Participants received a course of psychological therapy treatment in Improving Access to Psychological Therapies (IAPT) services between 2012 and 2019. Cox proportional hazards models were run to test associations between improvement in depression following psychological therapy and incidence of dementia diagnosis up to eight years later. RESULTS: Improvements in depression following treatment were associated with reduced rates of dementia diagnosis up to 8 years later (HR = 0.88, 95% CI 0.83-0.94), after adjustment for key covariates. Strongest effects were observed for vascular dementia (HR = 0.86, 95% CI 0.77-0.97) compared with Alzheimer's disease (HR = 0.91, 95% CI 0.83-1.00). CONCLUSIONS: Reliable improvement in depression across psychological therapy was associated with reduced incidence of future dementia. Results are consistent with at least two possibilities. Firstly, psychological interventions to improve symptoms of depression may have the potential to contribute to dementia risk reduction efforts. Secondly, psychological therapies may be less effective in people with underlying dementia pathology or they may be more likely to drop out of therapy (reverse causality). Tackling the under-representation of older people in psychological therapies and optimizing therapy outcomes is an important goal for future research

Developing a digital intervention for cancer survivors: an evidence-, theory- and person-based approach

This paper illustrates a rigorous approach to developing digital interventions using an evidence-, theory- and person-based approach. Intervention planning included a rapid scoping review which identified cancer survivors’ needs, including barriers and facilitators to intervention success. Review evidence (N=49 papers) informed the intervention’s Guiding Principles, theory-based behavioural analysis and logic model. The intervention was optimised based on feedback on a prototype intervention through interviews (N=96) with cancer survivors and focus groups with NHS staff and cancer charity workers (N=31). Interviews with cancer survivors highlighted barriers to engagement, such as concerns about physical activity worsening fatigue. Focus groups highlighted concerns about support appointment length and how to support distressed participants. Feedback informed intervention modifications, to maximise acceptability, feasibility and likelihood of behaviour change. Our systematic method for understanding user views enabled us to anticipate and address important barriers to engagement. This methodology may be useful to others developing digital interventions

Metabolic syndrome, psychological status and quality of life in obesity: the QUOVADIS Study

Objective: We aimed to investigate the association of the clinical variables of the metabolic syndrome (MS) and psychological parameters on health-related quality of life (HRQL) in obesity. In particular, our aim was to investigate the relative impact of physical symptoms, somatic diseases and psychological distress on both the physical and the mental domains of HRQL. Design: Cross-sectional study. Subjects: A cohort of 1822 obese outpatients seeking treatment in medical centers. Measurements: HRQL was measured by the standardized summary scores for physical (PCS) and mental (MCS) components of the Short Form 36 Health Survey (SF-36). Patients were grouped according to tertiles of PCS and MCS. Metabolic and psychological profiles of PCS and MCS tertiles were compared by discriminant analysis. Results: The profile of metabolic and psychological variables was tertile-specific in 62.4 and 68.3% of patients in the lowest and highest tertiles of PCS, respectively, while concordance was low in the mid-tertile (32.8%). Concordance was very high in the lowest (74.4%) and in the highest (75.5%) tertiles of MCS, and was fair in the mid-tertile (53.2%). The main correlates of PCS were obesity-specific and general psychological well-being, BMI, body uneasiness, binge eating, gender and psychiatric distress. Only hypertension and hyperglycemia qualified as correlates among the components of MS. The components of MS did not define MCS. Conclusions: Psychological well-being is the most important correlate of HRQL in obesity, both in the physical and in the mental domains, whereas the features of MS correlate only to some extent with the physical domain of HRQL

Salivary cortisol in longitudinal associations between affective symptoms and midlife cognitive function: a British birth cohort study

Affective disorders are associated with accelerated cognitive ageing. However, current understanding of biological mechanisms which underlie these observed associations is limited. The aim of this study was to test: 1) Whether cortisol acts as a pathway in the association between depressive or anxiety symptoms across adulthood and midlife cognitive function; 2) Whether cortisol is associated with later depressive or anxiety symptoms, and cognitive function. Data were used from the National Child Development Study (NCDS), a sample of infants born in mainland UK during one week of 1958. A measure of the accumulation of affective symptoms was derived from data collected from age 23 to 42 using the Malaise Inventory Scale. Salivary cortisol measures were available at age 44–45. Cognitive function (memory, fluency, information processing) and affective symptoms were assessed at the age of 50. Path models were run to test whether salivary cortisol explained the longitudinal association between depressive or anxiety disorder symptoms and cognitive function. Direct effects of affective symptoms are shown across early to middle adulthood on cognitive function in midlife (memory and information processing errors). However, there were no effects of affective symptoms on cognitive function through cortisol measures. Additionally, cortisol measures were not significantly associated with subsequent affective symptoms or cognitive function at the age of 50. These results do not provide clear evidence to suggest that cortisol plays a role in the association between affective symptoms and cognitive function over this period of time. These findings contribute to our understanding of how the association between affective symptoms and cognitive function operates over time