A randomised controlled trial evaluating two cognitive rehabilitation approaches for cancer survivors with perceived cognitive impairment.

PURPOSE: Up to 70% of survivors report cognitive symptoms after chemotherapy. We compared two cognitive rehabilitation programs to a control group in cancer survivors. METHODS: Study population were adult cancer survivors with cognitive symptoms 6-60 months after adjuvant chemotherapy. Participants randomised to: Attention Process Training (APT), Compensatory Strategy Training (CST), or control group. Active interventions comprised 6-week, 2-h/week small group sessions. ASSESSMENTS: pre- and post-intervention, 6- and 12-months later. Primary outcome was change in cognitive symptoms (FACT-COG-PCI subscale) between baseline and post-intervention. Secondary endpoints included objective neuropsychological performance, Functional Impact Assessment (FIA), patient-reported outcome measures, and associations. Analyses were on an intention-to-treat basis. Analysis of covariance mixed models were used for continuous outcomes. RESULTS: Sixty-five participants were randomised (APT n = 21; CST n = 24; controls n = 20): 94% breast cancer, median age 54. Median time since chemotherapy 20.7 months. FACT-COG-PCI, clinical neuropsychological T-scores, and FIA improved in all groups over time, but no significant differences between arms. On mean neuropsychological T-scores 19/65 (29%) were impaired at baseline; post-intervention impairment controls 31.3%, CST 16.7%, APT 20.0%. On FIA at baseline, nine were impaired; this decreased to three post-intervention (one/group). FACT-COG-PCI was weakly associated with neuropsychological tests (rho = 0.24, p = 0.051) at baseline, and had no association with FIA. Neuropsychological total mean T-score was moderately positively associated with FIA (rho = 0.37, p = 0.003). CONCLUSION: There were no significant differences between intervention groups and controls using linear mixed models adjusted for baseline scores. IMPLICATIONS FOR CANCER SURVIVORS: Cognitive symptoms and neuropsychological test scores improve over time.

Lack of cognitive impairment in long-term survivors of colorectal cancer.

BACKGROUND: Our longitudinal study reported cognitive impairment in 43% of people following diagnosis of localised colorectal cancer (CRC) versus 15% in healthy controls (p < 0.001) and 50% versus 13% 1-2 years later (p < 0.001). Here we evaluate cognitive function and neuroimaging in a subgroup at long-term follow-up. PATIENTS AND METHODS: Cancer-free Australian participants in the study, and controls, completed cognitive and functional assessments. Neuroimaging was optional. Blood tests included inflammatory markers, clotting factors, sex hormones and apolipoprotein E genotype. The primary endpoint was demographically and practice effect-corrected cognitive scores comparing CRC survivors with controls over time examined using a linear mixed model, adjusted for baseline performance. Secondary endpoints included cognitive impairment rate using the Global Deficit Score [GDS > 0.5], Functional Deficit Score, blood results and neuroimaging. RESULTS: The study included 25 CRC survivors (60% men, median age 72) at mean 9 years after baseline (9 received adjuvant chemotherapy) and 25 controls (44% men, median age 68) at mean 6 years after baseline. There were no significant differences in cognitive scores or proportion with cognitive impairment (16 vs. 8%) between survivors and controls and no evidence of accelerated ageing in CRC survivors. Baseline cognitive performance predicted for subsequent cognitive function. There were no differences in functional tests or blood tests between groups. In 18 participants undergoing neuroimaging, 10 CRC survivors had higher myoinositol levels than 8 controls, and lower volume in the right amygdala and caudate and left hippocampal regions. CONCLUSIONS: There was no difference in cognitive capacity and function between CRC survivors and controls 6-12 years after diagnosis. Differences in neuroimaging require confirmation in a larger sample. HIGHLIGHTS: • No evidence of long term cognitive impairment in colorectal cancer survivors compared to controls 6-12 years after diagnosis • No evidence of accelerated cognitive ageing in colorectal cancer survivors • No evidence of long-term functional impairment in colorectal cancer survivors.

On the receiving end: have patient perceptions of the side-effects of cancer chemotherapy changed since the twentieth century?

BACKGROUND: Studies in 1983 and 1993 identified and ranked symptoms experienced by cancer patients receiving chemotherapy. We repeated the studies to obtain updated information on patient perceptions of chemotherapy-associated symptoms. PATIENTS AND METHODS: A cross-sectional interview and patient-reported outcome questionnaires were administered to out-patients receiving chemotherapy. Patients selected from 124 cards to identify and rank the severity of physical and non-physical symptoms they had experienced and attributed to chemotherapy (primary endpoint). The patient's medical oncologist and primary chemotherapy nurse were invited to rank the five symptoms they believed the patient would rank as their most severe. We analysed the association of symptoms and their severity with patient demographics, chemotherapy regimen, and patient-reported outcomes. Results were compared to the earlier studies. RESULTS: Overall, 302 patients completed the interview: median age 58 years (range 17-85); 56% female; main tumour types colorectal 81 (27%), breast 67 (22%), lung 49 (16%); 45% treated with curative intent. Most common symptoms (reported by >50%) were: alopecia, general weakness, effects on family/partner, loss of taste, nausea, fatigue, difficulty sleeping, effects on work/home duties, and having to put life on hold. The most severe symptoms (ranked by >15% in top five) were: concern about effects on family/partner, nausea, fear of the future, fatigue, not knowing what will happen, putting my life on hold, and general weakness. Perceptions of doctors and nurses of patients' symptom severity closely matched patients' rankings. CONCLUSIONS: Compared to earlier studies, there was an increase in non-physical concerns such as effects on family and future, and a decrease in physical symptoms, particularly vomiting, but nausea, fatigue and general weakness remained bothersome. HIGHLIGHTS: • Symptoms related to chemotherapy have changed over time, likely due to less toxic regimens and improvements in supportive care. • Effects on family/partner, fear of the future, not knowing what will happen, and "life on hold" were major issues for patients. • Vomiting has decreased but nausea, fatigue and general weakness remain common symptoms for chemotherapy patients.

Neurocognitive Function and Quality of Life Outcomes in the ONTRAC Study for Skin Cancer Chemoprevention by Nicotinamide.

Nicotinamide (vitamin B3) has photoprotective effects and reduces skin cancer incidence in high risk patients. Nicotinamide also improves cognition in animal models. As part of the ONTRAC (Oral Nicotinamide To Reduce Actinic Cancer) phase III placebo-controlled, randomized trial to assess nicotinamide's efficacy in skin cancer prevention, we included clinical neurocognitive function and patient-reported quality of life assessments at baseline and after 12 months of intervention in individuals with previous skin cancer in order to assess any effect of oral nicotinamide (500 mg po twice daily) on cognitive function and quality of life. In our sample of 310 participants who completed neurocognitive function testing at baseline and at 12 months, we were not able to detect any significant effect of oral nicotinamide on cognitive function nor on quality of life. Further studies of nicotinamide's effects on cognition in humans might include individuals with pre-existing mild cognitive impairment, and it may be that higher doses of nicotinamide are required to significantly influence cognitive function compared to doses required to reduce skin cancer.

Prognostic indices of inflammatory markers, cognitive function and fatigue for survival in patients with localised colorectal cancer.

BACKGROUND: Inflammation promotes the development of malignancy, while a variety of systemic markers of inflammation predict for worse cancer outcomes including recurrence and survival. Here, we evaluate the prognostic impact of cytokine concentrations, full blood count (FBC) differential ratios, cognitive function and fatigue on survival in patients with localised colorectal cancer (CRC). PATIENTS AND METHODS: Data are from a prospective longitudinal study comparing cognitive function and fatigue in patients with CRC who did (n=173) and did not (n=116) receive adjuvant/neoadjuvant chemotherapy. Baseline blood results (prior to any chemotherapy) included cytokines and FBC from which neutrophil lymphocyte ratio, lymphocyte monocyte ratio, platelet lymphocyte ratio and platelet monocyte ratio were derived. Fatigue was measured with the Functional Assessment of Cancer Therapy-Fatigue subscale and cognitive function by a neuropsychological test battery. Kaplan-Meier methods were used to estimate disease-free survival (DFS) and overall survival (OS). Univariable and multivariable Cox regression analyses were performed to evaluate factors potentially prognostic of outcomes. RESULTS: At a median follow-up of 91.2 months, 227 subjects (79%) are still alive, and 212 (73%) have no evidence of a recurrence. Five-year OS and DFS are 86% (95% CI 81% to 90%) and 77% (95% CI 71% to 82%), respectively. None of the cytokines (interleukin (IL-6), IL-1 and tumour necrosis factor) or differential ratios of blood components, fatigue or cognitive function was statistically related to DFS or OS. Patient educational status (P=0.018), stage of disease (P=0.032), alanine transaminase (P=0.003), lactate dehydrogenase (P=0.008) and carcinoembryonic antigen (P=0.002) were significant as prognostic covariates of OS in univariable analyses, with similar results for DFS. CONCLUSION: None of the a priori selected markers of inflammation, fatigue or cognitive function was associated with OS or DFS in this cohort of patients. TRIAL REGISTRATION NUMBER: NCT00188331, Post-results.

Perceived cognitive impairment in people with colorectal cancer who do and do not receive chemotherapy.

PURPOSE: Cognitive symptoms are common after cancer, but poorly associated with neuropsychological results. We previously reported colorectal cancer (CRC) patients had more cognitive impairment than controls. Here, we explore relationships between cognitive symptoms and neuropsychological domains. METHODS: Subjects with CRC (N = 362) and 72 healthy controls completed neuropsychological assessments and Functional Assessment of Cancer Therapy-Cognition (FACT-COG) at baseline (pre-chemotherapy) and 6, 12, and 24 months. Associations between neuropsychological and FACT-COG scores were explored: perceived cognitive impairment (PCI), perceived cognitive ability (PCA), impact of PCI on quality of life (CogQOL). RESULTS: Of 362 CRC subjects, 289 had loco-regional disease and 173 received chemotherapy (CTh+). At baseline, groups did not differ on total FACT-COG, PCI, or PCA scores. All scores, except PCA, were worse at 6 months in CTh+. CRC patients not receiving chemotherapy did not differ from controls on FACT-COG domains. PCA associated weakly (r = 0.28-0.34) with attention/executive function, visual memory, and global deficit score. There was no association between PCI and neuropsychological domains. Fatigue, anxiety/depression, and poorer quality of life were associated with PCI and CogQOL (r = 0.44-0.51) in CRC patients. CONCLUSIONS: No association was seen between total FACT-COG or PCI, and neuropsychological domains. A weak-moderate association was found between PCA and attention/executive function and visual memory. TRIAL REGISTRATION: The study was registered with clinicaltrials.gov (trial registration: NCT00188331). IMPLICATIONS FOR CANCER SURVIVORS: Cognitive symptoms are associated with fatigue, anxiety/depression, and poorer quality of life, and do not appear to be related to actual cognitive performance. Rates were lower than that reported in breast cancer survivors. Cognitive symptoms were greatest in those who received chemotherapy, with no significant difference between the non-chemotherapy survivors and healthy controls.

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

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 significant effect of chemotherapy. Attention/working memory, verbal learning/memory, and complex processing speed were most affected. Cognitive impairment was similar in patients with localized and metastatic CRC. Cytokine levels were elevated in patients with CRC compared with HCs. There was no association between overall cognitive function and fatigue, quality of life, anxiety/depression, or any blood test. Cognitive symptoms at 12 months were reported in 25% of patients with localized CRC versus 17% of HCs (P = .19). More participants who received chemotherapy had cognitive symptoms at 6 months (32%) versus those who did not (16%; P = .007), with no significant difference at 12 months (29% v 21%, respectively; P = .19). Objective cognitive function was only weakly associated with cognitive symptoms. CONCLUSION: Patients with CRC had substantially more cognitive impairment at every assessment than HCs, with no significant added effect of chemotherapy. Mechanisms of cognitive impairment remain unknown.