Showing papers by "Haryana M. Dhillon published in 2015"

A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention

Abstract: BackgroundNonmelanoma skin cancers, such as basal-cell carcinoma and squamous-cell carcinoma, are common cancers that are caused principally by ultraviolet (UV) radiation. Nicotinamide (vitamin B3) has been shown to have protective effects against damage caused by UV radiation and to reduce the rate of new premalignant actinic keratoses. MethodsIn this phase 3, double-blind, randomized, controlled trial, we randomly assigned, in a 1:1 ratio, 386 participants who had had at least two nonmelanoma skin cancers in the previous 5 years to receive 500 mg of nicotinamide twice daily or placebo for 12 months. Participants were evaluated by dermatologists at 3-month intervals for 18 months. The primary end point was the number of new nonmelanoma skin cancers (i.e., basal-cell carcinomas plus squamous-cell carcinomas) during the 12-month intervention period. Secondary end points included the number of new squamous-cell carcinomas and basal-cell carcinomas and the number of actinic keratoses during the 12-month inte...

Cognitive Function in Patients With Colorectal Cancer Who Do and Do Not Receive Chemotherapy: A Prospective, Longitudinal, Controlled Study

Abstract: Purpose Cognitive dysfunction is reported in people with cancer. Therefore, we evaluated longitudinal changes in cognitive function and underlying mechanisms in people with colorectal cancer (CRC) and healthy controls (HCs). Patients and Methods Participants completed cognitive assessments and questionnaires reporting cognitive symptoms, fatigue, quality of life, and anxiety/depression at baseline (before chemotherapy, if given) and 6, 12, and 24 months. Blood tests included cytokines, clotting factors, apolipoprotein E genotype, and sex hormones. Primary end point was overall cognitive function measured by the Global Deficit Score at 12 months. Results We recruited 289 patients with localized CRC (173 received chemotherapy; median age, 59 years; 63% male), 73 patients with limited metastatic/recurrent CRC, and 72 HCs. Cognitive impairment was more frequent in patients with localized CRC than HCs at baseline (43% v 15%, respectively; P < .001) and 12 months (46% v 13%, respectively; P < .001), with no sig...

Nicotinamide and neurocognitive function.

Abstract: Nicotinamide, or vitamin B3, is a precursor of nicotinamide adenine dinucleotide (NAD+) and is involved in a multitude of intra- and inter-cellular processes, which regulate some of the cell's metabolic, stress, and immune responses to physiological or pathological signals. As a precursor of NAD+, which is a key coenzyme in the production of adenosine triphosphate or cellular energy, nicotinamide has been investigated for potential neuroprotective effects in cellular, animal, and human studies.ObjectivesWe aimed to summarize the current evidence on the effect of dietary and supplemental nicotinamide on cognitive function.MethodsA literature review was conducted on the effects of nicotinamide and its derivatives as a preventive and therapeutic agent for disorders of neurocognitive function. Specific conditions examined include age-related cognitive decline, Alzheimer's disease, Parkinson's disease, and ischaemic and traumatic brain injury.ResultsData from animal and human interventional studies and...

First interim analysis of a randomised trial of whole brain radiotherapy in melanoma brain metastases confirms high data quality

Abstract: Brain metastases are a common cause of death in patients with melanoma. The role of adjuvant whole brain radiotherapy (WBRT) following local treatment of intracranial melanoma metastases is controversial. The Australian and New Zealand Melanoma Trials Group (ANZMTG) and the Trans-Tasman Radiation Oncology Group (TROG) are leading the first ever single histology randomised trial investigating this question. The primary endpoint is distant intracranial failure on magnetic resonance imaging (MRI) within twelve months of randomisation. The first planned interim analysis was performed twelve months after randomisation of the 100th patient. The analysis was an opportunity to review completeness of the trial data to date. All data received up to the end of twelve months after randomisation of the 100th patient was reviewed. Review of pathology reports confirmed that all 100 patients had stage IV melanoma and were appropriately entered into the study. Of the 47 distant intracranial events, 34 occurred in isolation (i.e. only distant failure was identified), whilst 13 were accompanied by local failure. Data review showed compliance with the protocol mandated MRI schedule and accuracy of intracranial failure reporting was very high. The Quality of Life (QoL) component of the study achieved a 91% completion rate. For the neurocognitive function (NCF) assessments, a high completion rate was maintained throughout the 12 month period. Where assessments were not performed at expected time points, valid reasons were noted. Radiotherapy quality was high. Of 50 patients who received WBRT, 32 were reviewed as per protocol design and there was only one major variation out of 308 data points reviewed (0.3%). There were minimal trial related adverse events (AEs) and no serious adverse events (SAEs). Pre-specified protocol stopping rules were not met. The Data Safety Monitoring Committee (DSMC) recommended the trial continue recruitment after reviewing the unblinded data. The data provision and quality to date indicates that a reliable outcome will be obtained when the final analysis is performed. Accrual is ongoing with 156 out of 200 patients randomised to date (26th November 2014).

Oral nicotinamide to reduce actinic cancer: A phase 3 double-blind randomized controlled trial.

Abstract: 9000 Background: Nicotinamide (vitamin B3) enhances DNA repair and prevents cutaneous immune suppression after ultraviolet (UV) radiation exposure. It reduces photocarcinogenesis in mice, and human...

Editorial: Psychosocial Advances in Neuro-Oncology.

Abstract: Neuro-oncology is a complex field encompassing scientific and clinical developments in the diagnosis and management of cancers directly affecting the central nervous system (CNS). These include brain tumors and metastases, and non-CNS cancers and treatments that produce neurocognitive impairment. To date, the dominant focus of neuro-oncology literature has been on the biological mechanisms and neurocognitive effects of brain tumor and cancer. However, neurocognitive impairments and psychological disorders arise from an interaction between physiological, medical, and psychosocial factors (1). Therefore, to guide holistic models of care, a biopsychosocial perspective is needed (2). Psychosocial aspects of care focus on how people perceive and react to their diagnosis and symptoms and the ways in which they cope with their illness within their social context. Subjective reports of symptoms are often more closely related to quality of life than objective indices, such as neuropsychological test performance (2). High rates of depression and anxiety have been consistently reported in neuro-oncology samples, with distress found to persist or even increase over time (3). Due to the increased emphasis on outpatient care, family members assume the primary role in supporting individuals to cope with symptoms and the everyday impact of their illness. Cancer can place strain on relationships and compromise the physical and mental health of family members, in turn impacting their ability to provide sustained support to the person with cancer (4). This Research Topic aims to enhance understanding of the neurocognitive and psychosocial consequences of neuro-oncological disorders. It also aims to showcase advances in supportive care and highlight future research priorities for this population. The neurocognitive consequences of cancer were the focus of three articles. A meta-analysis by Ono and co-authors found overall evidence that adjuvant chemotherapy for breast cancer is associated with subtle cognitive impairment. To strengthen the evidence base, they recommended that future prospective longitudinal research examine cognitive impairment levels before and after chemotherapy, with comparisons made to pre-diagnosis functioning. Robinson and co-authors posed the question of whether screening tools, such as the Montreal Cognitive Assessment (MoCA), are sufficiently sensitive to the cognitive effects of brain tumor. Their findings suggested that a brief but tailored assessment may have greater sensitivity to detect mild or focal effects. Dwan and colleagues examined whether rates of cognitive impairment after brain tumor vary according to source of reference used (i.e., norms, controls, and premorbid functioning). Reassuringly, comparisons showed that rates of impairment were largely consistent across sources. They advocated for a multi-faceted neuropsychological test battery with a measure of estimated premorbid cognitive functioning to avoid over- or under-estimation of impairment. Behavioral and social consequences of brain tumor were the topic of two articles led by Simpson and Ownsworth. Simpson and co-authors identified that rates of behavioral changes after brain tumor were variable based on both self-report (7–40%) and relative report (8–60%), and were higher for people with seizures and poorer functional status. Routine assessment and multi-level management of behavioral concerns was recommended. Qualitative research by Ownsworth and co-authors investigated family caregivers’ experiences of support and relationship changes. Due to the many issues found to impact on caregiver perceptions, it was recommended that professionals explore caregivers’ expectations and preferences for support throughout the illness. Psychological well-being after brain tumor was the key theme of two articles. Trad and colleagues used the Distress Thermometer to screen for distress in different groups of patients and caregivers at initial diagnosis and tumor recurrence. The high rate of distress in the patient and caregiver groups at both time points underscores the key role of neuro-oncology care coordinators in providing access to psychosocial support throughout the care continuum. In their perspective article, Ownsworth and Nash emphasized the importance of assessing existential well-being or people’s sense of meaning, purpose, and value in life, in addition to mood and distress levels. Different avenues of existential support were discussed for facilitating the meaning making process across the illness trajectory. Supportive care interventions for the neuro-oncology population were a focus of five articles, including two intervention studies. Jones and co-authors piloted a telephone-based psychological support intervention for people with brain tumor. The results of their single-case research provided preliminary support for the feasibility and utility of tele-based therapy for enhancing mental health and quality of life. A larger controlled trial is needed to examine factors influencing the efficacy of tele-based therapy. King and Green evaluated the efficacy of group cognitive rehabilitation for cancer survivors in a randomized controlled trial. Their findings generally supported the efficacy of their group intervention, with gains most apparent for perceived cognitive impairment. In a systematic review of interventions to improve information provision for brain tumor patients, Langbecker and Janda found that most studies reported high rates of satisfaction with information provision. However, few examined improvements in knowledge and the methodological quality was generally low. A scoping review of psychotherapy interventions by Kangas similarly highlighted the paucity of evidence-based interventions for managing anxiety and depressive symptoms for this population. Cormie and colleagues considered the potential for exercise interventions to counteract the broader consequences of cancer, including fatigue, cognitive impairment, depression, and anxiety. Their perspective article discusses the benefits of targeted exercise programs for patients with CNS cancers and the need for research that examines both safety and efficacy of interventions. In the final article of this Research Topic, Chambers and colleagues present an overview of the challenges and strategies for integrating quality standards of psychosocial care into neuro-oncology. They call for the development of a comprehensive model of survivorship care for people affected by brain tumor and their families. Overall, the development and evaluation of psychological and supportive care interventions for people with neuro-oncological illness is an area of emerging research and of high interest to health professionals working in the field. International quality standards stipulate the need for cancer care facilities to provide assessments of patient distress and appropriate interventions (5). This practical and evidence-based text provides a unique and timely resource on the psychosocial care needs of people with neuro-oncological conditions and emerging intervention approaches.

The impact of physical activity on fatigue and quality of life in lung cancer patients: A randomised controlled trial (RCT).

Abstract: 9507 Background: Physical activity (PA) has been shown to improve fatigue and quality of life (QOL) in a range of cancer populations. Little research has been done in the advanced lung cancer setti...

Cancer survivorship - an overview

Abstract: The number of people living after a diagnosis of cancer has grown with increasing rates of diagnosis, improved treatments and better supportive care. While more people are treated and live longer, many experience poorer general health outcomes, higher rates of comorbidities and complex late or long-lasting effects of their treatments. How the healthcare system, healthcare professionals and the broader community can work together to support those affected by cancer to achieve optimal health outcomes for the duration of their lives is a salient question.

Evaluation of a web-based cognitive rehabilitation programme (CRP) in cancer survivors reporting cognitive symptoms following chemotherapy.

Abstract: 9510 Background: Self-reported cognitive impairment is frequently seen in cancer survivors. We evaluated a CRP in cancer patients with cognitive symptoms. Methods: 243 adult cancer patients who had...