Understanding the incidence, duration, and severity of symptoms through daily symptom monitoring among frail and non-frail older patients receiving metastatic prostate cancer treatments.

INTRODUCTION: Older adults with metastatic prostate cancer (mPC) experience high symptom burden associated with treatment. Frailty may exacerbate treatment toxicity. The aim of this study was to explore short-term treatment toxicity in patients with metastatic prostate cancer. MATERIALS AND METHODS: Older adults with metastatic prostate cancer starting chemotherapy, androgen-receptor-axis targeted therapies, or radium-223 participated in a prospective, multicentre, observational study. Participants self-reported symptoms daily using the Edmonton Symptom Assessment System for one treatment cycle via internet or telephone. The most common moderate-to-severe symptoms (score≥4), their duration, and the proportion of participants who experienced improvements in symptom severity (score<4) after reporting moderate-to-severe symptoms at baseline were determined using descriptive statistics. Once-weekly symptom questionnaires were administered and analyzed using linear mixed effect models. Symptom incidence, duration, and frailty associations were assessed using t-tests and chi-square tests. RESULTS: Ninety participants completed the study (mean age=77 years [standard deviation=6.1], 42% frail [Vulnerable Elders Survey≥3]). The most common moderate-to-severe symptoms across cohorts were fatigue (46.8%), insomnia (42.9%), poor wellbeing (41.2%), pain (37.5%), and decreased appetite (37.1%). Poor wellbeing had a higher incidence in frail participants (62.5% in frail vs. 31.4% in non-frail, p=0.039). Symptom duration varied across cohorts and between frail and non-frail participants. Among participants who reported moderate-to-severe symptoms at baseline, no more than 15% improved in any symptom. There were statistically significant improvements in weekly symptoms for fatigue, decreased appetite, and insomnia in the chemotherapy cohort only. DISCUSSION: Limitations include a short follow-up duration, lack of a control group, and few radium-223 participants. Regular symptom monitoring can help clinicians understand temporal patterns and durations of symptoms and inform supportive care approaches.

Effectiveness of geriatric assessment and management in older cancer patients: a systematic review and meta-analysis.

BACKGROUND: Frailty and multimorbidity among older cancer patients affect treatment tolerance and efficacy. Comprehensive geriatric assessment and management is recommended to optimize cancer treatment, but its effect on various outcomes remains uncertain. OBJECTIVE: Our objective was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) and cost-effectiveness studies comparing comprehensive geriatric assessment (with or without implementation of recommendations) to usual care in older cancer patients. METHODS: We searched MEDLINE, EMBASE, CINAHL, and Cochrane trials from inception to January 27, 2023, for RCTs and cost-effectiveness studies. Pooled estimates for outcomes were calculated using random-effects models. RESULTS: A total of 19 full-text articles representing 17 RCTs were included. Average participant age was 72-80 years, and 31%-62% were female. Comprehensive geriatric assessment type, mode of delivery, and evaluated outcomes varied across studies. Meta-analysis revealed no difference in risk of mortality (risk ratio [RR] = 1.08. 95% confidence interval [CI] = 0.91 to 1.29), hospitalization (RR = 0.92, 95% CI = 0.77 to 1.10), early treatment discontinuation (RR = 0.89, 95% CI = 0.67 to 1.19), initial dose reduction (RR = 0.99, 95% CI = 0.99 to 1.26), and subsequent dose reduction (RR = 0.87, 95% CI = 0.70 to 1.09). However, the risk of treatment toxicity was statistically significantly lower in the comprehensive geriatric assessment group (RR = 0.78, 95% CI = 0.70 to 0.86). No cost-effectiveness studies were identified. CONCLUSION: Compared with usual care, comprehensive geriatric assessment was not associated with a difference in risk of mortality, hospitalization, treatment discontinuation, and dose reduction but was associated with a lower risk of treatment toxicity indicating its potential to optimize cancer treatment in this population. Further research is needed to evaluate cost-effectiveness.

Implementing geriatric assessment and management for older Canadians with cancer: Adherence to and satisfaction with the intervention, results of the 5C study.

INTRODUCTION: Geriatric assessment and management (GAM) is recommended by professional organizations and recently several randomized controlled trials (RCTs) demonstrated benefits in multiple health outcomes. GAM typically leads to one or more recommendations for the older adult on how to optimize their health. However, little is known about how well recommendations are adhered to. Understanding these issues is vital to designing GAM trials and clinical programs. Therefore, the aim of this study was to examine the number of GAM recommendations made and adherence to and satisfaction with the intervention in a multicentre RCT of GAM for older adults with cancer. MATERIALS AND METHODS: The 5C study was a two-group parallel RCT conducted in eight hospitals across Canada. Each centre kept a detailed recruitment and retention log. The intervention teams documented adherence to their recommendations. Medical records were also reviewed to assess which recommendations were adhered to. Twenty-three semi-structured interviews were conducted with 12 members of the intervention teams and 11 oncology team members to assess implementation of the study and the intervention. RESULTS: Of the 350 participants who were enrolled, 173 were randomized to the intervention arm. Median number of recommendations was seven. Mean adherence to recommendations based on the GAM was 69%, but it varied by type of recommendation, ranging from 98% for laboratory tests to 28% for psychosocial/psychiatry oncology referrals. There was no difference in the number of recommendations or non-adherence to recommendations by sex, level of frailty, or functional status. Oncologists and intervention team members were satisfied with the study implementation and intervention delivery. DISCUSSION: Adherence to recommendations was variable. Adherence to laboratory investigations and further imaging were generally high but much lower for recommendations regarding psychosocial support. Further collaborative work with older adults with cancer is needed to understand how to optimize the intervention to be consistent with patient goals, priorities, and values to ensure maximal impact on health outcomes.

Daily physical activity monitoring in older adults with metastatic prostate cancer on active treatment: Feasibility and associations with toxicity.

INTRODUCTION: Physical activity may be associated with cancer treatment toxicity, but generalizability to geriatric oncology is unclear. As many older adults have low levels of physical activity and technology use, this area needs further exploration. We evaluated the feasibility of daily step count monitoring and the association between step counts and treatment-emergent symptoms. MATERIALS AND METHODS: Adults aged 65+ starting treatment (chemotherapy, enzalutamide/abiraterone, or radium-223) for metastatic prostate cancer were enrolled in a prospective cohort study. Participants reported step counts (measured via smartphone) and symptoms (Edmonton Symptom Assessment Scale) daily for one treatment cycle (i.e., 3-4 weeks). Embedded semi-structured interviews were performed upon completion of the study. The feasibility of daily monitoring was evaluated with descriptive statistics and thematic analysis. The predictive validity of a decline in daily steps (compared to pre-treatment baseline) for the emergence of symptoms was examined using sensitivity and positive predictive value (PPV). Associations between a 15% decline in steps and the emergence of moderate (4-6/10) to severe (7-10/10) symptoms and pain in the next 24 h were assessed using logistic regression. RESULTS: Of 90 participants, 47 engaged in step count monitoring (median age = 75, range = 65-88; 52.2% participation rate). Daily physical activity monitoring was found to be feasible (94% retention rate; 90.5% median response rate) with multiple patient-reported benefits including increased self-awareness and motivation to engage in physical activity. During the first treatment cycle, instances of a 15% decline in steps were common (n = 37, 78.7%), as was the emergence of moderate to severe symptoms overall (n = 40, 85.1%) and pain (n = 26, 55.3%). The predictive validity of a 15% decline in steps on the emergence of moderate to severe symptoms was good (sensitivity = 81.8%, 95% confidence interval [CI] = 68.7-95.0; PPV = 73.0%, 95% CI = 58.7-87.3), although the PPV for pain was poor (sensitivity = 77.8%, 95% CI = 58.6-97.0; PPV = 37.8%, 95% CI = 22.2-53.5). In the regression models, changes in daily physical activity were not associated with symptoms or pain. DISCUSSION: Changes in physical activity had modest ability to predict moderate to severe symptoms overall. Although participation was suboptimal, daily activity monitoring in older adults with cancer appears feasible and may have other uses such as improving physical activity levels. Further studies are warranted.

Validity of a self-administered G8 screening test for older patients with cancer.

INTRODUCTION: The Geriatric 8 (G8) is a brief cancer-specific tool which screens for patients who require a comprehensive geriatric assessment (CGA). The G8 test assesses patients on eight domains such as mobility, polypharmacy, age, and self-rated health. However, the current G8 requires a healthcare professional (nurse or physician) present to conduct the test, which limits its usefulness. The Self-G8 questionnaire (S-G8) is an adaptation of the original G8 test, assessing all the same domains, with questions modified to be appropriate for patients to self-complete. Our objective was to evaluate the performance of S-G8 compared to the G8 and CGA. MATERIALS AND METHODS: The initial S-G8 was designed by our team through review of the literature and questionnaire design principles, and was optimized through feedback from patients over the age of 70. The questionnaire subsequently underwent further refinement after undergoing pilot testing (N = 14). The diagnostic accuracy of the final iteration of the S-G8 was evaluated along with the standard G8 in a prospective cohort study (N = 52) in an academic geriatric oncology clinic at the Princess Margaret Cancer Centre, Toronto, Canada. Psychometric characteristics were evaluated including internal consistency, sensitivity, and specificity compared to the G8 and to the CGA. RESULTS: There was strong correlation between the G8 and S-G8 scores, with a Spearman correlation co-efficient of 0.76 (p < 0.001). Internal consistency was acceptable at 0.60. The frequency of abnormality (<14 score) for the G8 and S-G8 was 82.7% and 61.5%, respectively. The mean score for the original G8 and S-G8 was 11.9 and 13.5, respectively. The cut-off of 14 for the S-G8 yielded the best combination of sensitivity of 0.70 ± 0.07 and specificity of 0.78 ± 0.14 when compared to the G8. When compared to two or more abnormal domains on the CGA, the S-G8 performed at least as well as the G8 with a sensitivity of 0.77, specificity of 0.85, and a Youden's index of 0.62. DISCUSSION: The S-G8 questionnaire appears to be an acceptable alternative to the original G8 in identifying older adults with cancer who will benefit from a CGA. Large scale testing is warranted.

The impact of sarcopenia on clinical outcomes in men with metastatic castrate-resistant prostate cancer.

INTRODUCTION: Sarcopenia is common in men with metastatic castrate-resistant prostate cancer (mCRPC) and has been largely assessed opportunistically through computed-tomography (CT) scans, excluding measures of muscle function. Therefore, the impact of a comprehensive assessment of sarcopenia on clinical outcomes in men with mCRPC is poorly understood. The objectives of this study were to comprehensively assess sarcopenia through CT scans and measures of muscle function and examine its impact on severe treatment toxicity, time to first emergency room (ER) visit, disease progression, and overall mortality in men initiating chemotherapy or androgen receptor-targeted axis (ARAT) therapy for mCRPC. METHODS: This was a secondary analysis of a prospective observational study of men with mCRPC at the Princess Margaret Cancer Centre between July 2015-May 2021. Participants were classified as sarcopenic if they had CT-based low muscle mass or low muscle density, a grip strength and gait speed score of <35.5kg and <0.8m/s, respectively, prior to treatment initiation. The impact of sarcopenia on severe treatment toxicity was assessed using multivariable logistic regression. Multivariable Cox regression models were used to determine the impact of sarcopenia on risk of visiting the ER, prostate-specific antigen progression, radiographic progression, and overall mortality. RESULTS: A total of 110 men (mean age: 74.6) were included in the analysis. At baseline, 30 (27.3%) were classified as sarcopenic. Sarcopenia was a significant predictor of severe toxicity (aOR = 6.26, 95%CI = 1.17-33.58, P = 0.032) and ER visits (aHR = 4.41, 95%CI = 1.26-15.43, p = 0.020) in men initiating ARAT but not in men initiating chemotherapy. Sarcopenia was also a predictor of radiographic progression (aHR = 2.39, 95%CI = 1.06-5.36, p = 0.035) and overall mortality (aHR = 2.44, 95%CI = 1.17-5.08, p = 0.018) regardless of treatment type. CONCLUSIONS: Baseline sarcopenia predicts radiographic progression and overall mortality in men with mCRPC regardless of the type of treatment and may also predict severe treatment toxicity and ER visits in men initiating ARAT.

Impact of treatment on elder-relevant physical function and quality of life outcomes in older adults with metastatic castration-resistant prostate cancer.

INTRODUCTION: Understanding physical function (PF) and quality of life (QoL) treatment effects are important in treatment decision-making for older adults with cancer. However, data are limited for older men with metastatic castration-resistant prostate cancer (mCRPC). We evaluated the effects of treatment on PF and QoL in older men with mCRPC. MATERIALS AND METHODS: Men aged 65+ with mCRPC were enrolled in this multicenter prospective observational study. PF measures included instrumental activities of daily living, grip strength, chair stands, and gait speed. QoL measures included fatigue, pain, mood, and Functional Assessment of Cancer Therapy (FACT)-General total and sub-scale scores. Outcomes were collected at baseline, three, and six months. Linear mixed effects regression models were used to examine PF and QoL differences over time across various treatment cohorts. RESULTS: We enrolled 198 men starting chemotherapy (n = 71), abiraterone (n = 37), enzalutamide (n = 67), or radium-223 (n = 23). At baseline, men starting chemotherapy had worse measures of PF, QoL, pain, and mood than the other groups. Over time, all PF measures remained stable, pain improved, but functional wellbeing (FWB) and mood worsened significantly for all cohorts. However, change over time in all outcomes was not appreciably different between treatment cohorts. Worst-case sensitivity analyses identified attrition (ranging from 22 to 42% by six months) as a major limitation of our study, particularly for the radium-223 cohort. DISCUSSION: FWB and mood were most prone to deterioration over time, whereas pain improved with treatment. Although patients initiating chemotherapy had worse baseline PF and QoL, chemotherapy was not associated with significantly greater worsening over time compared to other common therapies for mCRPC. These findings may assist in treatment discussions with patients. However, given the modest sample size, attrition, and timeframe of follow-up, the impact of treatment on PF and QoL outcomes in this setting requires further study, particularly for radium-223.

Symptom experiences of older adults during treatment for metastatic prostate cancer: A qualitative investigation.

INTRODUCTION: Exploring symptom experiences of older men during metastatic prostate cancer treatment can help clinicians identify unmet supportive care needs that, if addressed, could improve toxicity management and enhance patient wellbeing. Previous qualitative studies of older adults with advanced prostate cancer have focused on the psychological experience rather than the overall symptom experience. Therefore, the objective of this study was to understand the lived experience of symptoms and supportive care needs in older men undergoing treatment for metastatic prostate cancer. MATERIALS AND METHODS: Semi-structured interviews were conducted with older adults (aged 65+) who completed their first cycle of chemotherapy, androgen-axis targeted therapies, or radium-223 for metastatic castrate-resistant and sensitive prostate cancer at the Princess Margaret Cancer Centre, Toronto, Canada. Six coders worked in pairs to review interview transcripts and conduct a thematic analysis. A consensus was reached through team discussions. Topics of interest included symptom experiences, the impact of symptoms on daily life, symptom management strategies, and suggestions for external support. RESULTS: Thirty-six interviews were conducted with older adults (mean age: 76 years, 92% with metastatic castrate-resistant prostate cancer) who started chemotherapy (n = 11), androgen-axis targeted therapies (n = 19), or radium-223 (n = 6). The most common treatment-specific symptoms included: fatigue, pain, sleep disturbances, mood disturbances, and gastrointestinal symptoms. Four themes on the impact of symptoms on daily life emerged: resting more than usual, changes in mobility, changes in maintaining activities of daily living, and not feeling up to most things. It is important to note that participants who underwent chemotherapy have previously completed other lines of treatment and had more advanced disease, possibly contributing to higher prevalence of symptoms and greater impact on daily life. Four themes on symptom management strategies emerged: positive support systems, seeking help, interventions by healthcare providers, and self-management strategies. Suggestions for external support included building social support networks, improving health literacy, improving continuity of care, receiving support from healthcare providers, engaging in health-seeking behaviours, and addressing unmet supportive care needs. DISCUSSION: Exploring symptom experiences of older men with metastatic prostate cancer provides valuable insights for developing supportive care programs and improving patient care.

Feasibility and acceptability of remote symptom monitoring (RSM) in older adults during treatment for metastatic prostate cancer.

INTRODUCTION: Emerging data support multiple benefits of remote symptom monitoring (RSM) during chemotherapy to improve outcomes. However, these studies have not focused on older adults and do not include treatments beyond chemotherapy. Although chemotherapy, androgen receptor axis-targeted therapies (ARATs), and radium-223 prolong survival, toxicities are substantial and increased in older adults with metastatic prostate cancer (mPC). We aimed to assess RSM feasibility among older adults receiving life-prolonging mPC treatments. MATERIALS AND METHODS: Older adults aged 65+ starting chemotherapy, an ARAT, or radium-223 for mPC were enrolled in a multicentre prospective cohort study. As part of the RSM package, participants completed the Edmonton Symptom Assessment Scale (ESAS) daily and detailed questionnaires assessing mood, anxiety, fatigue, insomnia, and pain weekly online or by phone throughout one treatment cycle (3-4 weeks). Alerts were sent to the clinical oncology team for severe symptoms (ESAS ≥7). Participants also completed an end of study questionnaire that assessed study burden and satisfaction. Descriptive statistics were used to determine recruitment and retention rates, participant response rates to daily and weekly questionnaires, clinician responses to alerts, and participant satisfaction rates. An inductive descriptive approach was used to categorize open-ended responses about study benefits, challenges, and recommendations into relevant themes. RESULTS: Ninety males were included (mean age 77 years, 48% ARAT, 38% chemotherapy, and 14% radium-223). Approximately 38% of patients preferred phone-based RSM. Patients provided RSM responses in 1216 out of 1311 daily questionnaires (93%). Over 93% of participants were satisfied (36%), very satisfied (43%), or extremely satisfied (16%) with RSM, although daily reporting was reported by several (8%) as burdensome. Nearly 45% of patients reported severe symptoms during RSM. Most symptom alerts sent to the oncology care team were acknowledged (97%) and 53% led to follow-ups with a nurse or physician for additional care. DISCUSSION: RSM is feasible and acceptable to older adults with mPC, but accommodation needs to be made for phone-based RSM. The optimal frequency and duration of RSM also needs to be established.

The role of frailty in modifying physical function and quality of life over time in older men with metastatic castration-resistant prostate cancer.

INTRODUCTION: As treatment options for metastatic castration-resistant prostate cancer (mCRPC) expand and its patient population ages, consideration of frailty is increasingly relevant. Using a novel frailty index (FI) and two common frailty screening tools, we examined quality of life (QoL) and physical function (PF) in frail versus non-frail men receiving treatment for mCRPC. MATERIALS AND METHODS: Men aged 65+ starting docetaxel chemotherapy, abiraterone, or enzalutamide for mCRPC were enrolled in a multicenter prospective cohort study. QoL, fatigue, pain, and mood were measured with the Functional Assessment of Cancer Therapy-General scale, the Edmonton Symptom Assessment System tiredness and pain subscales, and the Patient Health Questionnaire-9. PF was evaluated with grip strength, four-meter gait speed, five times Sit-to-Stand Test, and instrumental activities of daily living. Frailty was determined using the Vulnerable Elders Survey (VES-13), the Geriatric 8 (G8), and an FI constructed from 36 variables spanning laboratory abnormalities, geriatric syndromes, functional status, social support, as well as emotional, cognitive, and physical deficits. We categorized patients as non-frail (FI ≤ 0.2, VES < 3, G8 > 14), pre-frail (FI > 0.20, ≤0.35), or frail (FI > 0.35, VES ≥ 3, G8 ≤ 14); assessed correlation between the three tools; and performed linear mixed-effects regression analyses to examine longitudinal differences in outcomes (0, 3, 6 months) by frailty status. A sensitivity analysis with worst-case imputation was conducted to explore attrition. RESULTS: We enrolled 175 men (mean age 74.9 years) starting docetaxel (n = 71), abiraterone (n = 37), or enzalutamide (n = 67). Our FI demonstrated moderate correlation with the VES-13 (r = 0.607, p < 0.001) and the G8 (r = -0.520, p < 0.001). Baseline FI score was associated with worse QoL (p < 0.001), fatigue (p < 0.001), pain (p < 0.001), mood (p < 0.001), PF (p < 0.001), and higher attrition (p < 0.01). Over time, most outcomes remained stable, although pain improved, on average, regardless of frailty status (p = 0.007), while fatigue (p = 0.045) and mood (p = 0.015) improved in frail patients alone. DISCUSSION: Among older men receiving care for mCRPC, frailty may be associated with worse baseline QoL and PF, but over time, frail patients may experience largely similar trends in QoL and PF as their non-frail counterparts. Further study with larger sample size and longer follow-up may help elucidate how best to incorporate frailty into treatment decision-making for mCRPC.

Impact of Geriatric Assessment and Management on Quality of Life, Unplanned Hospitalizations, Toxicity, and Survival for Older Adults With Cancer: The Randomized 5C Trial.

PURPOSE: American Society of Clinical Oncology recommends that older adults with cancer being considered for chemotherapy receive geriatric assessment (GA) and management (GAM), but few randomized controlled trials have examined its impact on quality of life (QOL). PATIENTS AND METHODS: The 5C study was a two-group parallel 1:1 single-blind multicenter randomized controlled trial of GAM for 6 months versus usual oncologic care. Eligible patients were age 70+ years, diagnosed with a solid tumor, lymphoma, or myeloma, referred for first-/second-line chemotherapy or immunotherapy or targeted therapy, and had an Eastern Cooperative Oncology Group performance status of 0-2. The primary outcome QOL was measured with the global health scale of the European Organisation for the Research and Treatment of Cancer QOL questionnaire and analyzed with a pattern mixture model using an intent-to-treat approach (at 6 and 12 months). Secondary outcomes included functional status, grade 3-5 treatment toxicity; health care use; satisfaction; cancer treatment plan modification; and overall survival. RESULTS: From March 2018 to March 2020, 350 participants were enrolled. Mean age was 76 years and 40.3% were female. Fifty-four percent started treatment with palliative intent. Eighty-one (23.1%) patients died. GAM did not improve QOL (global QOL of 4.4 points [95% CI, 0.9 to 8.0] favoring the control arm). There was also no difference in survival, change in treatment plan, unplanned hospitalization/emergency department visits, and treatment toxicity between groups. CONCLUSION: GAM did not improve QOL. Most intervention group participants received GA on or after treatment initiation per patient request. Considering recent completed trials, GA may have benefit if completed before treatment selection. The COVID-19 pandemic may have affected our QOL outcome and intervention delivery for some participants.

Association of Chemotherapy, Enzalutamide, Abiraterone, and Radium 223 With Cognitive Function in Older Men With Metastatic Castration-Resistant Prostate Cancer.

Importance: Older adults are at greater risk of cognitive decline with various oncologic therapies. Some commonly used therapies for advanced prostate cancer, such as enzalutamide, have been linked to cognitive impairment, but published data are scarce, come from single-group studies, or focus on self-reported cognition. Objective: To longitudinally examine the association between cognitive function and docetaxel (chemotherapy), abiraterone, enzalutamide, and radium Ra 223 dichloride (radium 223) in older men with metastatic castration-resistant prostate cancer. Design, Setting, and Participants: A multicenter, prospective, observational cohort study was conducted across 4 academic cancer centers in Ontario, Canada. A consecutive sample of 155 men age 65 years or older with metastatic castration-resistant prostate cancer starting any treatment with docetaxel, abiraterone acetate, enzalutamide, or radium Ra 223 dichloride (radium 223) were enrolled between July 1, 2015, and December 31, 2019. Exposures: First-line chemotherapy (docetaxel), abiraterone, enzalutamide, or radium 223. Main Outcomes and Measures: Cognitive function was measured at baseline and end of treatment using the Montreal Cognitive Assessment, the Trail Making Test part A, and the Trail Making Test part B to assess global cognition, attention, and executive function, respectively. Absolute changes in scores over time were analyzed using univariate and multivariable linear regression, and the percentages of individuals with a decline of 1.5 SDs in each domain were calculated. Results: A total of 155 men starting treatment with docetaxel (n = 51) (mean [SD] age, 73.5 [6.2] years; 34 [66.7%] with some postsecondary education), abiraterone (n = 29) (mean [SD] age, 76.2 [7.2] years; 18 [62.1%] with some postsecondary education), enzalutamide (n = 54) (mean [SD] age, 75.7 [7.4] years; 33 [61.1%] with some postsecondary education), and radium 223 (n = 21) (mean [SD] age, 76.4 [7.2] years; 17 [81.0%] with some postsecondary education) were included. Most patients had stable cognition or slight improvements during treatment. A cognitive decline of 1.5 SDs or more was observed in 0% to 6.5% of patients on each measure of cognitive function (eg, 3 of 46 patients [6.5%; 95% CI, 2.2%-17.5%] in the group receiving chemotherapy [docetaxel] had a decline of 1.5 SDs for Trails A and Trails B). Although patients taking enzalutamide had numerically larger declines than those taking abiraterone, differences were small and clinically unimportant. Conclusions and Relevance: These findings suggest that most older men do not experience significant cognitive decline in attention, executive function, and global cognition while undergoing treatment for advanced prostate cancer regardless of the treatment used.

Examining the ability of the Cancer and Aging Research Group tool to predict toxicity in older men receiving chemotherapy or androgen-receptor-targeted therapy for metastatic castration-resistant prostate cancer.

BACKGROUND: Because multiple treatments are available for metastatic castrate-resistant prostate cancer (mCRPC) and most patients are elderly, the prediction of toxicity risk is important. The Cancer and Aging Research Group (CARG) tool predicts chemotherapy toxicity in older adults with mixed solid tumors, but has not been validated in mCRPC. In this study, its ability to predict toxicity risk with docetaxel chemotherapy (CHEMO) was validated, and its utility was examined in predicting toxicity risk with abiraterone or enzalutamide (A/E) among older adults with mCRPC. METHODS: Men aged 65+ years were enrolled in a prospective observational study at 4 Canadian academic cancer centers. All clinically relevant grade 2 to 5 toxicities over the course of treatment were documented via structured interviews and chart review. Logistic regression was used to identify predictors of toxicity. RESULTS: Seventy-one men starting CHEMO (mean age, 73 years) and 104 men starting A/E (mean age, 76 years) were included. Clinically relevant grade 3+ toxicities occurred in 56% and 37% of CHEMO and A/E patients, respectively. The CARG tool was predictive of grade 3+ toxicities with CHEMO, which occurred in 36%, 67%, and 91% of low, moderate, and high-risk groups (P = .003). Similarly, grade 3+ toxicities occurred among A/E users in 23%, 48%, and 86% with low, moderate, and high CARG risk (P < .001). However, it was not predictive of grade 2 toxicities with either treatment. CONCLUSIONS: There is external validation of the CARG tool in predicting grade 3+ toxicity in older men with mCRPC undergoing CHEMO and demonstrated utility during A/E therapy. This may aid with treatment decision-making.

Age-related cytokine effects on cancer-related fatigue and quality of life in acute myeloid leukemia.

OBJECTIVES: We determined whether cytokines are a potential target to improve cancer-related fatigue (CRF) and quality of life (QOL) in acute myeloid leukemia (AML). METHODS: 219 patients age 18+ undergoing intensive chemotherapy for AML were assessed at up to 4 time points (pre-treatment, 1 month, 6 months, 12 months). CRF and QOL were assessed with validated patient-reported outcome measures with minimum clinically important differences (MCID) of 4 and 10 points, respectively. A panel of 31 plasma cytokines was measured. CRF and QOL were regressed against scaled cytokine values, adjusting for age, gender, time, remission status, and hemoglobin in linear models. RESULTS: 498 cytokine samples were available. For CRF, the model R2 was 25.3%, with cytokines explaining 6.9% of the variance. For QOL, corresponding values were 27.9% and 7.4%, respectively. A shift from the 30th to 70th centile distribution of all cytokines was associated with an improvement in CRF by 5.2 points and a 10.2-point improvement in QOL. A shift from 5th to 95th centile in TNF-α but no other single cytokine was associated with a change of >MCID in CRF, but there was no similar association with QOL. Cytokines had greater explanatory power for CRF in older versus younger adults and the most influential cytokines differed by age, particularly TNF-α. CONCLUSION: Cytokines explain a relatively small amount of CRF and QOL scores in patients with AML and effects differ by age group. For cytokine-targeted therapies to improve either outcome, multiple cytokines may need to be substantially altered and therapeutic targets may vary with age.

Clinical and Cost-effectiveness of a Comprehensive geriatric assessment and management for Canadian elders with Cancer-the 5C study: a study protocol for a randomised controlled phase III trial.

INTRODUCTION: Geriatric assessment and management is recommended for older adults with cancer referred for chemotherapy but no randomised controlled trial has been completed of this intervention in the oncology setting. TRIAL DESIGN: A two-group parallel single blind multi-centre randomised trial with a companion trial-based economic evaluation from both payer and societal perspectives with process evaluation. PARTICIPANTS: A total of 350 participants aged 70+, diagnosed with a solid tumour, lymphoma or myeloma, referred for first/second line chemotherapy, who speak English/French, have an Eastern Collaborative Oncology Group Performance Status 0-2 will be recruited. All participants will be followed for 12 months. INTERVENTION: Geriatric assessment and management for 6 months. The control group will receive usual oncologic care. All participants will receive a monthly healthy ageing booklet for 6 months. OBJECTIVE: To study the clinical and cost-effectiveness of geriatric assessment and management in optimising outcomes compared with usual oncology care. RANDOMISATION: Participants will be allocated to one of the two arms in a 1:1 ratio. The randomisation will be stratified by centre and treatment intent (palliative vs other). OUTCOME: Quality of life. SECONDARY OUTCOMES: (1) Cost-effectiveness, (2) functional status, (3) number of geriatric issues successfully addressed, (4) grades3-5 treatment toxicity, (5) healthcare use, (6) satisfaction, (7) cancer treatment plan modification and (8) overall survival. PLANNED ANALYSIS: For the primary outcome we will use a pattern mixture model using an intent-to-treat approach (at 3, 6 and12 months). We will conduct a cost-utility analysis alongside this clinical trial. For secondary outcomes 2-4, we will use a variety of methods. ETHICS AND DISSEMINATION: Our study has been approved by all required REBs. We will disseminate our findings to stakeholders locally, nationally and internationally and by publishing the findings. TRIAL REGISTRATION NUMBER: NCT03154671.

Performance of the Vulnerable Elders Survey 13 screening tool in identifying cancer treatment modification after geriatric assessment in pre-treatment patients: A retrospective analysis.

PURPOSE: Geriatric assessment (GA) is recommended for older adults ≥ 70 years with cancer to guide treatment selection. Screening tools such as the Vulnerable Elders Survey (VES-13) and G6 have been used to identify patients at highest need of GA. Whether either tool predicts a change in oncologic treatment following GA is unclear. METHODS: Patients attending a geriatric oncology clinic between July 2015 and June 2017 who completed a VES-13 and underwent subsequent GA were included. Clinical information was extracted from a prospectively maintained database. G6 scores were assigned retrospectively. Patients were stratified into those who were "VES-13 positive" (score ≥ 3) and "VES-13 negative" (score < 3). Logistic regression was used to explore the relationship between VES-13 score, G6 score, and treatment modification. RESULTS: Ninety-nine patients were seen prior to initiating cancer treatment. The median VES-13 score was 7; with 81.8% of patients scoring ≥3. The treatment plan was modified in 47.5% of patients after GA. VES-13 score was predictive of treatment plan modification (63.0% among VES-13 positive versus 16.7% among VES-13 negative patients; p = 0.001). G6 performed similarly to the VES-13. The only statistically significant predictor of treatment change in multivariable analysis was performance status. CONCLUSION: VES-13 positive patients are more likely to undergo treatment modification to reduce treatment intensity or supportive care only. The VES-13 may provide oncologists with a rapid, reliable way of identifying vulnerability in older adults with cancer who may need further GA prior to commencing cancer treatment.

Healthy Bones Study: can a prescription coupled with education improve bone health for patients receiving androgen deprivation therapy?-a before/after study.

PURPOSE: To evaluate the ability of a multimodal patient education initiative to improve adherence to healthy bone behaviors (HBBs) in men with prostate cancer receiving androgen deprivation therapy (ADT). METHODS: This was a pilot prospective, single-site, before-and-after clinical trial. The control arm (n = 51) received routine care. The intervention arm (n = 52) received multimodal HBB education which included a healthy bones prescription (BoneRx), focused face-to-face education with an oncology nurse or physician, and customized educational materials. The primary endpoints were feasibility of study methods and self-reported adherence to HBBs (vitamin D intake ≥ 1000 IU/day, calcium intake 1000-1500 mg/day, and exercise ≥ 150 min/week) at 3-month follow-up. Secondary endpoints included receipt of bone mineral density (BMD) testing. RESULTS: Patients were satisfied with the study intervention, found educational materials easy to understand, and felt that it increased their knowledge about osteoporosis. Although the intervention appeared to be associated with trends toward improved levels of vitamin D intake (adjusted odds ratio [OR] 1.8, 95% confidence interval [CI] 0.74-4.5), calcium intake (OR 1.5, 95% CI 0.63-3.4), and exercise (OR 1.7, 0.75-3.9) as compared to the control arm, none of these were statistically significant. Patients who received the study intervention were more likely to receive BMD testing (OR 3.3, 95% CI 1.3-8.8). CONCLUSIONS: Although a brief, tailored educational intervention was feasible to implement and improve BMD test utilization, it did not increase HBB participation. Larger, well-designed trials are needed to clarify the effect of patient education interventions on HBB adherence. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT01973673 ).

Impact of Androgen Deprivation Therapy on Self-Reported Cognitive Function in Men with Prostate Cancer.

PURPOSE: Although androgen deprivation therapy is widely used to treat prostate cancer, its effects on cognitive function are unclear. To our knowledge no prior report has examined the impact of androgen deprivation therapy on self-reported cognitive function. MATERIALS AND METHODS: Three groups of men 50 years old or older who were matched on age and education were enrolled in the study, including 81 with prostate cancer starting on continuous androgen deprivation therapy, 84 controls with prostate cancer not receiving androgen deprivation therapy and 85 healthy controls. Two scales from the FACT-Cog (Functional Assessment of Cancer Therapy-Cognitive subscale) version 3 were used to assess self-reported cognitive function. Changes in cognitive scores with time were analyzed by 2 approaches, including 1) multivariable regression and 2) calculation of the proportion of subjects per group with a decrease of 1 SD or more. Multivariable regression was applied to assess predictors of a decline in self-reported cognitive function. We also examined relationships between the FACT-Cog and a neuropsychological battery of 15 tests. RESULTS: Mean participant age was 69 years (range 50 to 87). The mean educational level was 15 years (range 8 to 24). FACT-Cog scores were similar at baseline across the cohorts. Neither analytical approach revealed that androgen deprivation therapy was associated with changes in self-reported cognitive function on either FACT-Cog scale. Mood and fatigue correlated with changes in self-reported cognitive function. The relationship between self-reported and objective cognitive measures was weak (maximum Spearman correlation coefficient 0.14) and only 2 of 30 correlations were statistically significant. CONCLUSIONS: A total of 12 months of androgen deprivation therapy were not associated with self-reported cognitive function changes in older men with nonmetastatic prostate cancer.

Improving bone health in men with prostate cancer receiving androgen deprivation therapy: Results of a randomized phase 2 trial.

BACKGROUND: Strategies to improve bone health care in men receiving androgen deprivation therapy (ADT) are not consistently implemented. The authors conducted a phase 2 randomized controlled trial of 2 education-based models-of-care interventions to determine their feasibility and ability to improve bone health care. METHODS: A single-center parallel-group randomized controlled trial of men with prostate cancer who were receiving ADT was performed. Participants were randomized 1:1:1 to 1) a patient bone health pamphlet and brief recommendations for their family physician (BHP+FP); 2) a BHP and support from a bone health care coordinator (BHP+BHCC); or 3) usual care. The primary efficacy outcome was receipt of a bone mineral density (BMD) test within 6 months. Secondary efficacy outcomes included guideline-appropriate calcium and vitamin D use and bisphosphonate prescriptions for men at high fracture risk. Feasibility endpoints included recruitment, retention, satisfaction, contamination, and outcome capture. The main analysis used logistic regression with a 1-sided P of .10. The trial is registered at ClinicalTrials.gov (identifier NCT02043236). RESULTS: A total of 119 men were recruited. The BHP+BHCC strategy was associated with a greater percentage of men undergoing a BMD test compared with the usual-care group (78% vs 36%; P<.001). BMD ordering also was found to be increased with the BHP+FP strategy (58% vs 36%; P = .047). Both strategies were associated with higher percentages of patients using calcium and vitamin D, but only the BHP+FP arm was statistically significant (P = .039). No men were detected to be at high fracture risk. All but one feasibility endpoint was met. CONCLUSIONS: Educational strategies to improve bone health care appear feasible and are associated with improved BMD ordering in men receiving ADT. Cancer 2018;124:1132-40. © 2017 American Cancer Society.

Perceptions of Study Newsletters for Older Cancer Patients in Longitudinal Studies.

To date, no study has examined the value of providing study newsletters in educating and motivating participants taking part in longitudinal intervention studies and reducing attrition in studies. The study team examined perceptions and satisfaction towards study newsletters, and their potential benefits, in a population of older men with prostate cancer participating in two ongoing longitudinal trials. Two study newsletters issues were mailed out 4 months apart to prostate cancer patients participating in a bone health and/or exercise intervention trial. Participants (n = 133) were invited to complete an 18-item custom-designed survey examining perceptions towards and satisfaction with the newsletter, and provide feedback about what makes an ideal study newsletter. Analyses were primarily descriptive. Resources required to produce a study newsletter were also calculated. Of 133 participants, 83 usable surveys were returned (response rate 62.4%). The mean satisfaction rating for the newsletter was 8.5/10 (SD 1.9) (10 = highly satisfied). Seventy eight percent said the newsletter encouraged them to continue to participate in the study, and 93% indicated that providing such study newsletters should be optional (64%) or mandatory (29%). Each newsletter required 31 h of study personnel time (mostly research student) to produce. Study participants were very satisfied with the newsletter and the majority indicated that study newsletters should be a regular practice in all long-term studies and may improve participant retention. Producing a newsletter is a low-cost method of educating participants in longitudinal studies. Its impact on recruitment and retention should be examined in clinical trials.