Henriette Breunis

Impact of Androgen-Deprivation Therapy on Physical Function and Quality of Life in Men With Nonmetastatic Prostate Cancer

PURPOSE This prospective longitudinal study evaluated the effect of androgen deprivation therapy (ADT) on objective and self-reported physical function. PATIENTS AND METHODS Men with nonmetastatic prostate cancer (PC) starting continuous ADT were enrolled in this matched cohort study. Physical function was assessed with the 6-minute walk test (6MWT), grip strength, and the timed-up-and-go (TUG) test, representing endurance and upper and lower extremity strength, respectively. Quality of life (QOL) was measured with the Medical Outcomes Study Short-Form 36 (SF-36) questionnaire. Subjects were assessed at baseline, 3, 6, and 12 months. Two control groups (PC without ADT; no PC), matched on age, education, and baseline function were enrolled. Mixed effects regression models were fitted, adjusting for baseline covariates. RESULTS We enrolled 87 patients on ADT, 86 PC controls, and 86 healthy controls; groups were similar in age (mean, 69.1 years; range, 50 to 87) and physical function. The 6MWT distance remained stable in the ADT group (P = .96) but improved in both control groups (P < .05). Grip strength declined in the ADT group (P = .04), remained stable in PC controls (P = .31), and improved in healthy controls (P = .008). TUG scores remained stable over time and across groups (P > .10). The SF-36 physical function summary score declined in the ADT group (P < .001), but increased in both control groups (P < .001). Negative effects on outcomes were observed within 3 months of starting ADT and were generally independent of age. CONCLUSION Endurance, upper extremity strength, and physical components of QOL are affected within 3 months of starting ADT. Up-front exercise interventions to counteract these losses are warranted.

Impact of Androgen-Deprivation Therapy on Cognitive Function in Men With Nonmetastatic Prostate Cancer

PURPOSE To evaluate the effects of androgen-deprivation therapy (ADT) on cognitive function in men with nonmetastatic prostate cancer (PC). PATIENTS AND METHODS The following three groups of men age 50 years or older and matched on age and education were enrolled: patients with PC starting continuous ADT (n = 77), patients with PC not receiving ADT (PC controls, n = 82), and healthy controls (n = 82). A battery of 14 neuropsychological tests, examining eight cognitive domains, was administered at baseline, 6 months, and 12 months. Changes in cognitive scores over time were analyzed using the following three approaches: multivariable linear regression; the proportion of participants per group with 1 standard deviation (SD) or greater declines, and the proportion of participants who declined by at least 1.5 SD on two or more tests. RESULTS The mean age and education level of participants were 68.9 years (range, 50 to 87 years) and 15.4 years of education (range, 8 to 24 years), respectively. Adjusted for age and education, all three cohorts had similar cognitive scores at baseline other than in one test of working memory. In adjusted regressions, ADT use was not associated with significant changes in the domains of attention/processing speed, verbal fluency, verbal memory, visual memory, or cognitive flexibility at either 6 months (all P > .05) or 12 months (all P > .05). One test each of immediate memory (P = .029), working memory (P = .031), and visuospatial ability (P = .034) were worse among ADT users than controls at 12 months, but these findings were not confirmed using other analytic approaches. CONCLUSION There is no consistent evidence that 12 months of ADT use has an adverse effect on cognitive function in elderly men with PC.

A clinical trial of supervised exercise for adult inpatients with acute myeloid leukemia (AML) undergoing induction chemotherapy

Patients with acute myeloid leukemia (AML) receiving induction chemotherapy (IC) were enrolled in a supervised exercise intervention to determine safety, feasibility, and efficacy. Physical fitness measures, quality of life (QOL) and fatigue were assessed using standardized measures at baseline, post-induction, and post first consolidation. Retention was excellent, the intervention was safe, and efficacy estimates suggested benefits in physical fitness and QOL outcomes. Exercise is a safe, promising intervention for improving fitness and QOL in this patient population. These results provide a foundation for a randomized trial to better understand the impact of exercise during IC on clinically important outcomes.

Management of decreased bone mineral density in men starting androgen‐deprivation therapy for prostate cancer

To determine whether clinicians discuss bone‐specific side‐effects with patients on androgen‐deprivation therapy (ADT) for prostate cancer, or prescribe lifestyle and pharmacological interventions for low bone mineral density (BMD), as decreased BMD is a common side‐effect of ADT, leading to increased risk of fracture.

Older age is associated with similar quality of life and physical function compared to younger age during intensive chemotherapy for acute myeloid leukemia

We examined the quality of life (QOL) and physical function over the first three cycles of intensive chemotherapy in 103 newly diagnosed younger (18-59 years, n=64) and older adults (age 60 or older, n=39) with acute myeloid leukemia. Both QOL and physical function were worse than normative data. QOL was fairly stable over time and similar in both age groups, whereas physical function generally improved over time, although the improvement was somewhat greater in younger than older adults. Compared to younger adults, older adults tolerate intensive chemotherapy quite well from QOL and physical function perspectives.

Correlation between cytokine levels and changes in fatigue and quality of life in patients with acute myeloid leukemia

Cancer-related fatigue (CRF) is a major problem in patients with acute myeloid leukemia (AML) and may be mediated by circulating cytokines. We examined this relationship in 74 adult AML patients before and after the first cycle of induction chemotherapy. Plasma levels of 13 cytokines were measured via electrochemiluminescence. At baseline, potentially clinically important (r>0.30) correlations were seen between tumor necrosis factor (TNF)-α and fatigue (r=-0.336, p=0.017). Over time, correlations with fatigue were noted with TNF-α (r=-0.341, p=0.006) and interferon-inducible protein (IP)-10 (r=0.353, p=0.005). The link between IP-10 and fatigue is novel, implicating CXC chemokine pathways for CRF in hematologic malignancies.

Quality of life and physical function in adults treated with intensive chemotherapy for acute myeloid leukemia improve over time independent of age.

OBJECTIVES Intensive chemotherapy (IC) is the primary treatment of acute myeloid leukemia (AML) but is associated with significant toxicity, particularly in older adults. We characterized the impact of AML and its treatment on quality of life (QOL) and physical function in younger (age 18-59) and older (age 60+) patients with AML over 1year from diagnosis. MATERIALS AND METHODS AML patients undergoing IC without stem-cell transplant at two tertiary care centers were enrolled in a prospective, longitudinal study. Assessments were done pre-IC and at 7 time points over the next year. QOL, fatigue, and physical performance (grip strength, 2-minute walk test (2MWT), timed chair stands) were measured in all patients whereas daily function was measured only in older patients. Data were analyzed using mixed effects regression models. RESULTS 237 patients were recruited (140 younger and 97 older, 56% male). One-year survival was 79% and 60% among younger and older patients, respectively. For patients in remission, global QOL and fatigue improved significantly over time (p<0.001 for both); trends were similar between older and younger patients. Grip strength did not change over time (p=0.58) whereas both the 2MWT (p<0.001) and timed chair stands (p<0.001) improved significantly. Daily function improved significantly over time (p=0.003). CONCLUSIONS Survivors of AML in remission after IC achieve significant improvements in QOL, fatigue, and physical function over time with similar trajectories for older and younger patients. These data suggest that appropriately selected older patients do well following IC.

Long‐term impact of androgen‐deprivation therapy on physical function and quality of life

This study examined the impact of androgen‐deprivation therapy (ADT) on physical function and quality of life (QOL) over 36 months.

Impact of androgen deprivation therapy on depressive symptoms in men with nonmetastatic prostate cancer.

Up to 50% of prostate cancer (PC) patients receive androgen deprivation therapy (ADT), often for several years. Although depression has been reported after a diagnosis of PC, whether ADT leads to or worsens depression is not clear.

Levels of sex hormones have limited effect on cognition in older men with or without prostate cancer

Androgen deprivation therapy is commonly used to treat prostate cancer, but by lowering testosterone levels it may affect cognitive function. However, the relationship between testosterone and cognition remains unclear. We examined the relationship between sex hormones (total testosterone, bioavailable testosterone, and estradiol) and cognition in a cross-sectional study of 198 older men (mean age 69.2 years, median education 16 years) with and without prostate cancer, none of who had started androgen deprivation therapy. We found relationships between total testosterone and two of four measures of working memory. Similar relationships were found in regression analyses adjusted for age and education with both total testosterone and estradiol. Neither hormone was related to other cognitive domains, nor was bioavailable testosterone level. Although cognitive function was not generally related to sex hormone levels in older men, there may be a weak association with working memory. These results may help guide future studies.