Evaluation of a Web-Based Cognitive Rehabilitation Program in Cancer Survivors Reporting Cognitive Symptoms After Chemotherapy

Purpose: Cognitive impairment is reported frequently by cancer survivors. There are no proven treatments. We evaluated a cognitive rehabilitation program (Insight) and compared it with standard care in cancer survivors self-reporting cognitive symptoms. Patients and Methods: We recruited adult cancer survivors with a primary malignancy (excluding central nervous system malignancies) who had completed three or more cycles of adjuvant chemotherapy in the previous 6 to 60 months and reported persistent cognitive symptoms. All participants received a 30-minute telephone consultation and were then randomly assigned to the 15-week, home-based intervention or to standard care. Primary outcome was self-reported cognitive function (Functional Assessment of Cancer Therapy Cognitive Function [FACT-COG] perceived cognitive impairment [PCI] subscale): difference between groups after intervention (T2) and 6 months later (T3). Results: A total of 242 participants were randomly assigned: median age, 53 years; 95% female. The primary outcome of difference in FACT-COG PCI was significant, with less PCI in the intervention group at T2 (P < .001). This difference was sustained at T3 (P < .001). At T2, there was a significant difference in all FACT-COG subscales, favoring the intervention. Neuropsychological results were not significantly different between the groups at T2 or T3. There were significantly lower levels of anxiety/depression and fatigue in the intervention group at T2. There were significant improvements in stress in the intervention group at both time points. There was no significant difference in quality of life between the groups at T2, but the intervention group had better quality of life at T3. Conclusion: The intervention, Insight, led to improvements in cognitive symptoms compared with standard care. To our knowledge, this is the first large randomized controlled trial showing an improvement in self-reported cognitive function in cancer survivors, indicating that this intervention is a feasible treatment.Supported by the Cancer Council New South Wales, Friends of the Mater Foundation, a Cancer Institute New South Wales Clinical Fellowship (V.J.B.), a Clinical Oncology Society of Australia/Roche Hematology Oncology Targeted Therapies Fellowship (V.J.B.), a Pfizer Cancer Research Grant (V.J.B.), and by the National Breast Cancer Foundation (J.L.V.)

Whole brain radiotherapy (WBRT) after local treatment of brain metastases in melanoma patients: Statistical Analysis Plan

Background: The WBRTMel trial is a multinational, open-label, phase III randomised controlled trial comparing whole brain radiotherapy (WBRT) to observation following local treatment of one to three melanoma brain metastases with surgery and/or stereotactic irradiation. The primary trial endpoint was to determine the effect of adding WBRT to local treatment on distant intracranial control, and the secondary endpoints were neurocognitive function, quality of life (QoL), performance status, overall survival, death from intracranial causes, death from melanoma and cost-effectiveness. Objective: The objective of this update is to outline and publish the pre-determined statistical analysis plan (SAP) before the database lock and the start of analysis. Methods: The SAP describes basic analysis principles, methods for dealing with a range of commonly encountered data analysis issues and the specific statistical procedures for analysing efficacy and safety outcomes. The SAP was approved after closure of recruitment and before completion of patient follow-up. It outlines the planned primary analyses and a range of subgroup and sensitivity analyses regarding the clinical and QoL outcomes. Health economic outcomes are not included in this plan but will be analysed separately. The SAP will be adhered to for the final data analysis of this trial to avoid analysis bias arising from knowledge of the data. Results: The resulting SAP is consistent with best practice and will allow open and transparent reporting. Conclusion: We have developed a SAP for the WBRTMel trial which will be followed to ensure high-quality standards of internal validity to minimise analysis bias

Whole brain radiotherapy after local treatment of brain metastases in melanoma patients - a randomised phase III trial

<p>Abstract</p> <p>Background</p> <p>Cerebral metastases are a common cause of death in patients with melanoma. Systemic drug treatment of these metastases is rarely effective, and where possible surgical resection and/or stereotactic radiosurgery (SRS) are the preferred treatment options. Treatment with adjuvant whole brain radiotherapy (WBRT) following neurosurgery and/or SRS is controversial. Proponents of WBRT report prolongation of intracranial control with reduced neurological events and better palliation. Opponents state melanoma is radioresistant; that WBRT yields no survival benefit and may impair neurocognitive function. These opinions are based largely on studies in other tumour types in which assessment of neurocognitive function has been incomplete.</p> <p>Methods/Design</p> <p>This trial is an international, prospective multi-centre, open-label, phase III randomised controlled trial comparing WBRT to observation following local treatment of intracranial melanoma metastases with surgery and/or SRS. Patients aged 18 years or older with 1-3 brain metastases excised and/or stereotactically irradiated and an ECOG status of 0-2 are eligible. Patients with leptomeningeal disease, or who have had previous WBRT or localised treatment for brain metastases are ineligible. WBRT prescription is at least 30 Gy in 10 fractions commenced within 8 weeks of surgery and/or SRS. Randomisation is stratified by the number of cerebral metastases, presence or absence of extracranial disease, treatment centre, sex, radiotherapy dose and patient age. The primary endpoint is the proportion of patients with distant intracranial failure as determined by MRI assessment at 12 months. Secondary end points include: survival, quality of life, performance status and neurocognitive function.</p> <p>Discussion</p> <p>Accrual to previous trials for patients with brain metastases has been difficult, mainly due to referral bias for or against WBRT. This trial should provide the evidence that is currently lacking in treatment decision-making for patients with melanoma brain metastases. The trial is conducted by the Australia and New Zealand Melanoma Trials Group (ANZMTG-study 01-07), and the Trans Tasman Radiation Oncology Group (TROG) but international participation is encouraged. Twelve sites are open to date with 43 patients randomised as of the 31st March 2011. The target accrual is 200 patients.</p> <p>Trial registration</p> <p>Australia and New Zealand Clinical Trials Register (ANZCTR): <a href="http://www.anzctr.org.au/ACTRN12607000512426.aspx">ACTRN12607000512426</a></p

The impact of physical activity on fatigue and quality of life in lung cancer patients: a randomised controlled trial protocol

Background: People with lung cancer have substantial symptom burden and more unmet needs than the general cancer population. Physical activity (PA) has been shown to positively influence quality of life (QOL), fatigue and daily functioning in the curative treatment of people with breast and colorectal cancers and lung diseases, as well as in palliative settings. A randomised controlled trial (RCT) is needed to determine if lung cancer patients benefit from structured PA intervention. The Physical Activity in Lung Cancer (PAL) trial is designed to evaluate the impact of a 2-month PA intervention on fatigue and QOL in patients with non-resectable lung cancer. Biological mechanisms will also be studied.Methods/design: A multi-centre RCT with patients randomised to usual care or a 2-month PA programme, involving supervised PA sessions including a behavioural change component and home-based PA. QOL questionnaires, disease and functional status and body composition will be assessed at baseline, 2, 4 and 6 months follow-up. The primary endpoint is comparative levels of fatigue between the 2 arms. Secondary endpoints include: QOL, functional abilities and physical function. Exploratory endpoints include: anxiety, depression, distress, dyspnoea, PA behaviour, fitness, hospitalisations, survival, cytokines and insulin-like growth factor levels.Discussion: This study will provide high-level evidence of the effect of PA programmes on cancer-related fatigue and QOL in patients with advanced lung cancer. If positive, the study has the potential to change care for people with cancer using a simple, inexpensive intervention to improve their QOL and help them maintain independent function for as long as possible.Trial registration: Australian New Zealand Clinical Trials Registry No. ACTRN12609000971235. © 2012 Dhillon et al.; licensee BioMed Central Ltd

Correlates of cognitive impairment in adult cancer survivors who have received chemotherapy and report cognitive problems

Objective Cognitive impairment negatively affects some cancer survivors who have completed chemotherapy; however, factors underlying this cognitive impairment remain poorly understood. We aimed to investigate (1) the relative importance of demographics, medical, and psychological characteristics associated with cognitive impairment and (2) the specific variables associated with cognitive impairment in adult cancer survivors who completed adjuvant chemotherapy. Methods We performed post hoc analyses of baseline data from early-stage cancer survivors with cognitive complaints who received adjuvant chemotherapy 0.5-5 years earlier and volunteered for a trial designed to improve cognition. The primary outcome of self-reported cognitive impairment was measured using a questionnaire; secondary outcome of objective cognitive impairment was measured using a computerized neuropsychological test battery. Hierarchical linear regression determined the relative importance of demographics, medical, and psychological characteristics in associations with both self-reported and objective cognitive impairment. Results The sample was 95% female and 89% breast cancer patients. The final model accounted for 33% of variation in self-reported cognitive impairment (n = 212, demographics 5%, medical 3%, and psychological 25%), with fatigue and stress as significant individual correlates (pvalues <= 0.0001). For the secondary analysis, the final model accounted for 19% of variation in objective cognitive impairment (n = 206, demographics 10%, medical 5%, and psychological 4%), with age, smoking history, and number of chemotherapy cycles as significant individual correlates. Conclusion We found that psychological characteristics are more important than demographic and medical characteristics in self-reported cognitive impairment, whereas other characteristics are more important in objective cognitive impairment. This suggests clinicians should investigate possible psychological problems in cancer survivors who self-report cognitive impairment.12 month embargo; published online: 14 July 2020This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Baseline quality of life is associated with survival among people with advanced lung cancer

Introduction: Lung cancer patients presenting with advanced cancer face low survival rates and a high symptom burden. There have been mixed findings for the association between survival and various patient reported outcomes (PROs). Methods: We used prospective data from 111 lung cancer patients with advanced stage III/IV disease to investigate the association of survival with PROs (European Organization for Research and Treatment of Cancer Core-30 and Lung Module). Cox proportional hazard models were used to examine the individual association between several PRO measures and survival. Results: Pain in chest and global quality of life (QoL) were found to have the strongest association with survival with a 20% increased hazard of death per 10% increase in pain in chest and 14% decrease in hazard of death per 10% increase in global QoL. Conclusion: Our results provide more evidence for the value of PRO data to inform clinical and patient decision-making.12 month embargo; published online: 15 May 2020This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Screening for cognitive symptoms among cancer patients during chemotherapy: Sensitivity and specificity of a single item self-report cognitive change score

Objectives: Cognitive symptoms are commonly reported among cancer patients and survivors, yet guidance on when self-reported cognitive symptoms warrant follow-up is lacking. We sought to establish cut-off scores for identifying patients with perceived low cognitive functioning on widely used self-report measures of cognition and a novel single item Cognitive Change Score. Methods: Adult patients diagnosed with invasive cancer who had completed at least one cycle of chemotherapy completed a questionnaire containing the EORTC-Cognitive Function (CF) subscale, Functional Assessment of Cancer Therapy-Cognitive Function (FACT-COG) Perceived Cognitive Impairment (PCI) and our Cognitive Change Score (CCS). We used receiver operating characteristic analyses to establish the discriminative ability of these measures against the Patient's Assessment of Own Functioning Inventory (PAOFI) as our reference standard. We chose cut-off scores on each measure that maximised both sensitivity and specificity for identifying patients with self-reported low CF. Results: We recruited 294 participants (55.8% women, mean age 56.6 years) with mixed cancer diagnoses (25.5 months since diagnosis). On the CCS, 77.6% reported some cognitive change since starting chemotherapy. On the PAOFI 36% had low CF. The following cut-off scores identified cases of low CF: ≥28.5 on the CCS (75.5% sensitivity, 67.6% specificity); ≤75.0 on the European Organisation for Research and Treatment of Cancer, QLQ-C30 Cognitive Functioning scale (90.9% sensitivity, 57.1% specificity); ≤55.1 on the FACT-COG PCI-18 (84.8% sensitivity, 76.2% specificity), and ≤59.5 on the FACT-COG PCI-20 (78.8% sensitivity, 84.1% specificity). Conclusions: We found a single item question asking about cognitive change has acceptable discrimination between patients with self-reported normal and low CF when compared to other more comprehensive self-report measures of cognitive symptoms. Further validation work is required.Open access articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Effects of Endocrine Therapy on Cognitive Function in Patients with Breast Cancer: A Comprehensive Review

Endocrine therapy forms the backbone of systemic therapy for the majority of persons with early and late-stage breast cancer. However, the side effects can negatively affect quality of life, and impact treatment adherence and overall oncological outcomes. Adverse effects on cognition are common, underreported and challenging to manage. We aim to describe the nature, incidence, risk factors and underlying mechanisms of endocrine therapy-induced cognitive dysfunction. We conducted a comprehensive literature review of the studies reporting on cognitive dysfunction associated with endocrine therapies for breast cancer. We also summarise prevention and treatment strategies, and ongoing research. Given that patients are taking endocrine therapies for longer durations than ever before, it is essential that these side effects are managed pro-actively within a multi-disciplinary team in order to promote adherence to endocrine therapy and improve patients&rsquo; quality of life

Low dose aspirin blocks breast cancer-induced cognitive impairment in mice.

Cancer patients with non-central nervous system tumors often suffer from cognitive impairment. While chemotherapy has long been attributed as the cause of these memory, learning and concentration difficulties, we recently observed cognitive impairment in cancer patients prior to treatment. This suggests the cancer alone may be sufficient to induce cognitive impairment, however the mechanisms are unknown. Here, we show that we can experimentally replicate the clinical phenomenon of cancer-associated cognitive impairment and we identify inflammation as a causal mechanism. We demonstrate that a peripheral tumor is sufficient to induce memory loss. Using an othotopic mouse model of breast cancer, we found that mice with 4T1.2 or EO771 mammary tumors had significantly poorer memory than mice without tumors. Memory impairment was independent of cancer-induced sickness behavior, which was only observed during the later stage of cancer progression in mice with high metastatic burden. Tumor-secreted factors were sufficient to induce memory impairment and pro-inflammatory cytokines were elevated in the plasma of tumor-bearing mice. Oral treatment with low-dose aspirin completely blocked tumor-induced memory impairment without affecting tumor-induced sickness or tumor growth, demonstrating a causal role for inflammation in cognitive impairment. These findings suggest that anti-inflammatories may be a safe and readily translatable strategy that could be used to prevent cancer-associated cognitive impairment in patients