Donna L. Berry

Intermittent versus Continuous Androgen Deprivation in Prostate Cancer

BACKGROUND Castration resistance occurs in most patients with metastatic hormone-sensitive prostate cancer who are receiving androgen-deprivation therapy. Replacing androgens before progression of the disease is hypothesized to prolong androgen dependence. METHODS Men with newly diagnosed, metastatic, hormone-sensitive prostate cancer, a performance status of 0 to 2, and a prostate-specific antigen (PSA) level of 5 ng per milliliter or higher received a luteinizing hormone-releasing hormone analogue and an antiandrogen agent for 7 months. We then randomly assigned patients in whom the PSA level fell to 4 ng per milliliter or lower to continuous or intermittent androgen deprivation, with patients stratified according to prior or no prior hormonal therapy, performance status, and extent of disease (minimal or extensive). The coprimary objectives were to assess whether intermittent therapy was noninferior to continuous therapy with respect to survival, with a one-sided test with an upper boundary of the hazard ratio of 1.20, and whether quality of life differed between the groups 3 months after randomization. RESULTS A total of 3040 patients were enrolled, of whom 1535 were included in the analysis: 765 randomly assigned to continuous androgen deprivation and 770 assigned to intermittent androgen deprivation. The median follow-up period was 9.8 years. Median survival was 5.8 years in the continuous-therapy group and 5.1 years in the intermittent-therapy group (hazard ratio for death with intermittent therapy, 1.10; 90% confidence interval, 0.99 to 1.23). Intermittent therapy was associated with better erectile function and mental health (P<0.001 and P=0.003, respectively) at month 3 but not thereafter. There were no significant differences between the groups in the number of treatment-related high-grade adverse events. CONCLUSIONS Our findings were statistically inconclusive. In patients with metastatic hormone-sensitive prostate cancer, the confidence interval for survival exceeded the upper boundary for noninferiority, suggesting that we cannot rule out a 20% greater risk of death with intermittent therapy than with continuous therapy, but too few events occurred to rule out significant inferiority of intermittent therapy. Intermittent therapy resulted in small improvements in quality of life. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00002651.).

Enhancing Patient-Provider Communication With the Electronic Self-Report Assessment for Cancer: A Randomized Trial

PURPOSE Although patient-reported cancer symptoms and quality-of-life issues (SQLIs) have been promoted as essential to a comprehensive assessment, efficient and efficacious methods have not been widely tested in clinical settings. The purpose of this trial was to determine the effect of the Electronic Self-Report Assessment-Cancer (ESRA-C) on the likelihood of SQLIs discussed between clinicians and patients with cancer in ambulatory clinic visits. Secondary objectives included comparison of visit duration between groups and usefulness of the ESRA-C as reported by clinicians. PATIENTS AND METHODS This randomized controlled trial was conducted in 660 patients with various cancer diagnoses and stages at two institutions of a comprehensive cancer center. Patient-reported SQLIs were automatically displayed on a graphical summary and provided to the clinical team before an on-treatment visit (n = 327); in the control group, no summary was provided (n = 333). SQLIs were scored for level of severity or distress. One on-treatment clinic visit was audio recorded for each participant and then scored for discussion of each SQLI. We hypothesized that problematic SQLIs would be discussed more often when the intervention was delivered to the clinicians. RESULTS The likelihood of SQLIs being discussed differed by randomized group and depended on whether an SQLI was first reported as problematic (P = .032). Clinic visits were similar with regard to duration between groups, and clinicians reported the summary as useful. CONCLUSION The ESRA-C is the first electronic self-report application to increase discussion of SQLIs in a US randomized clinical trial.

Depression screening using the Patient Health Questionnaire-9 administered on a touch screen computer

Objective: To (1) evaluate the feasibility of touch screen depression screening in cancer patients using the Patient Health Questionnaire‐9 (PHQ‐9), (2) evaluate the construct validity of the PHQ‐9 using the touch screen modality, and (3) examine the prevalence and severity of depression using this screening modality.

Quality of Life and Pain in Advanced Stage Prostate Cancer: Results of a Southwest Oncology Group Randomized Trial Comparing Docetaxel and Estramustine to Mitoxantrone and Prednisone

PURPOSE Palliation of bone pain can be achieved in men with androgen-independent prostate cancer treated with docetaxel and estramustine (DE) or mitoxantrone and prednisone (MP). While Southwest Oncology Group trial 99-16 demonstrated a survival improvement of DE over MP, the study also was designed to compare the palliation of disease-related symptoms. METHODS Pain palliation and global quality of life (QOL) were the two primary patient-reported outcomes. Pain was measured with the Present Pain Intensity scale of the McGill Pain Questionnaire-Short Form. The European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire C30 (QLQ-C30) and its Prostate Cancer Module (PR25) measured QOL and symptom status. Pain and analgesic use were measured at random assignment, every cycle for eight cycles, and 1 year from random assignment; the QLQ-C30 and the PR25 were administered at random assignment, before cycle four (week 10) and cycle eight (month 6) and at 1 year. In addition to the primary intent-to-treat, missing at random analysis, sensitivity analyses were performed to assess robustness of global QOL conclusions under alternative informative missing data assumptions. RESULTS Six hundred seventy four eligible patients received DE (n = 338) or MP (n = 336). In an intention-to-treat analysis, median overall survival was 17.5 months for the DE arm and 15.6 months for the MP arm (P = .02). There were no statistically significant differences in pain palliation between the treatment arms. The sensitivity analyses showed a consistent lack of statistically significant global QOL differences for the two arms. CONCLUSION DE had superior clinical efficacy (overall survival, time-to-progression, and prostate-specific antigen declines) with similar global QOL and pain palliation in the MP arm.

Phase III Trial of Selenium to Prevent Prostate Cancer in Men with High-grade Prostatic Intraepithelial Neoplasia: SWOG S9917

The threat of prostate cancer and the significant and often negative impact of its treatment underscore the importance of prevention. High-grade prostatic intraepithelial neoplasia (HGPIN) has been identified as a potential premalignant lesion marking an increased risk of prostate cancer and substantial evidence suggests that men with HGPIN are in need of prostate cancer prevention. In vitro, in vivo, epidemiologic, and clinical trial evidence that selenium supplementation protects against prostate cancer motivated the study we report here: a double-blind, randomized, placebo-controlled trial of selenium 200 (μg/d) as selenomethionine in men with HGPIN. The primary endpoint was progression of HGPIN to prostate cancer over a 3-year period. This National Cancer Institute Intergroup trial was coordinated by the Southwest Oncology Group (SWOG). Of 619 enrolled patients, 423 randomized men with HGPIN (212 selenium and 211 placebo) were eligible (by central pathology review) and included in the primary analysis. Three-year cancer rates were 36.6% (placebo) versus 35.6% (selenium; P = 0.73, adjusted). The majority of patients who developed cancer on trial (70.8%, selenium and 75.5%, placebo) had a Gleason score of 6 or less than 6; there were no differences in Gleason scores between the two arms. Subset analyses included the finding of a nonsignificantly reduced prostate cancer risk (relative risk = 0.82; 95% CI: 0.40–1.69) in selenium versus placebo patients in the lowest quartile of baseline plasma selenium level (<106 ng/mL). Overall, and in all other subsets defined by baseline blood selenium levels, selenium supplementation had no effect on prostate cancer risk. The 36% prostate cancer rate in men with HGPIN indicates the association of this lesion with an elevated prostate cancer risk. Future study in this setting should focus on selenium-deficient populations and selenium pharmacogenetics. Cancer Prev Res; 4(11); 1761–9. ©2011 AACR.

Electronic Self-Report Assessment for Cancer and Self-Care Support: Results of a Multicenter Randomized Trial

PURPOSE The purpose of this trial was to evaluate the effect of a Web-based, self-report assessment and educational intervention on symptom distress during cancer therapy. PATIENTS AND METHODS A total of 752 ambulatory adult participants were randomly assigned to symptom/quality-of-life (SxQOL) screening at four time points (control) versus screening, targeted education, communication coaching, and the opportunity to track/graph SxQOL over time (intervention). A summary of the participant-reported data was delivered to clinicians at each time point in both groups. All participants used the assessment before a new therapeutic regimen, at 3 to 6 weeks and 6 to 8 weeks later, completing the final assessment at the end of therapy. Change in Symptom Distress Scale-15 (SDS-15) score from pretreatment to end of study was compared using analysis of covariance and regression analysis adjusting for selected variables. RESULTS We detected a significant difference between study groups in mean SDS-15 score change from baseline to end of study: 1.27 (standard deviation [SD], 6.7) in the control group (higher distress) versus -0.04 (SD, 5.8) in the intervention group (lower distress). SDS-15 score was reduced by an estimated 1.21 (95% CI, 0.23 to 2.20; P = .02) in the intervention group. Baseline SDS-15 score (P < .001) and clinical service (P = .01) were predictive. Multivariable analyses suggested an interaction between age and study group (P = .06); in subset analysis, the benefit of intervention was strongest in those age > 50 years (P = .002). CONCLUSION Web-based self-care support and communication coaching added to SxQOL screening reduced symptom distress in a multicenter sample of participants with various diagnoses during and after active cancer treatment. Participants age > 50 years, in particular, may have benefited from the intervention.

Computerized symptom and quality-of-life assessment for patients with cancer part II: acceptability and usability.

PURPOSE/OBJECTIVES To determine the acceptability and usability of a computerized quality-of-life (QOL) and symptom assessment tool and the graphically displayed QOL and symptom output in an ambulatory radiation oncology clinic. DESIGN Descriptive, cross-sectional. SETTING Radiation oncology clinic located in an urban university medical center. SAMPLE 45 patients with cancer being evaluated for radiation therapy and 10 clinicians, who submitted 12 surveys. METHODS Acceptability of the computerized assessment was measured with an online, 16-item, Likert-style survey delivered as 45 patients undergoing radiation therapy completed a 25-item QOL and symptom assessment. Usability of the graphic output was assessed with clinician completion of a four-item paper survey. MAIN RESEARCH VARIABLES Acceptability and usability of computerized patient assessment. FINDINGS The patient acceptability survey indicated that 70% (n = 28) liked computers and 10% (n = 4) did not. The program was easy to use for 79% (n = 26), easy to understand for 91% (n = 30), and enjoyable for 71% (n = 24). Seventy-six percent (n = 25) believed that the amount of time needed to complete the computerized survey was acceptable. Sixty-six percent (n = 21) responded that they were satisfied with the program, and none of the participants chose the very dissatisfied response. Eighty-three percent (n = 10) of the clinicians found the graphic output helpful in promoting communication with patients, 75% (n = 9) found the output report helpful in identifying appropriate areas of QOL deficits or concerns, and 83% (n = 10) indicated that the output helped guide clinical interactions with patients. CONCLUSIONS The computer-based QOL and symptom assessment tool is acceptable to patients, and the graphically displayed QOL and symptom output is useful to radiation oncology nurses and physicians. IMPLICATIONS FOR NURSING Wider application of computerized patient-generated data can continue in various cancer settings and be tested for clinical and organizational outcomes.

Computerized symptom and quality-of-life assessment for patients with cancer part I: development and pilot testing.

PURPOSE/OBJECTIVES To develop and test an innovative computerized symptom and quality-of-life (QOL) assessment for patients with cancer who are evaluated for and treated with radiation therapy. DESIGN Descriptive, longitudinal prototype development and cross-sectional clinical data. SETTING Department of radiation oncology in an urban, academic medical center. SAMPLE 101 outpatients who were evaluated for radiation therapy, able to communicate in English (or through one of many interpreters available at the University of Washington), and competent to understand the study information and give informed consent. Six clinicians caring for the patients in the sample were enrolled. METHODS Iterative prototype development was conducted using a standing focus group of clinicians. The software was developed based on survey markup language and implemented in a wireless, Web-based format. Patient participants completed the computerized assessment prior to consultation with the radiation physician. Graphical output pages with flagged areas of symptom distress or troublesome QOL issues were made available to consulting physicians and nurses. MAIN RESEARCH VARIABLES Pain intensity, symptoms, QOL, and demographics. INSTRUMENTS Computerized versions of a 0 to 10 Pain Intensity Numerical Scale (PINS), Symptom Distress Scale, and Short Form-8. FINDINGS Focus group recommendations included clinician priorities of brevity, flexibility, and simplicity for both input interface and output and that the assessment output contain color graphic display. Patient participants included 45 women and 56 men with a mean age of 52.7 years (SD = 13.8). Fewer than half of the participants (40%) reported using a computer on a regular basis (weekly or daily). Completion time averaged 7.8 minutes (SD = 3.7). Moderate to high levels of distress were reported more often for fatigue, pain, and emotional issues than for other symptoms or concerns. CONCLUSIONS Computerized assessment of cancer symptoms and QOL is technically possible and feasible in an ambulatory cancer clinic. A wireless, Web-based system facilitates access to results and data entry and retrieval. The symptom and QOL profiles of these patients new to radiation therapy were comparable to other samples of outpatients with cancer. IMPLICATIONS FOR NURSING The ability to capture an easily interpreted illustration of a patients symptom and QOL experience in less than 10 minutes is a potentially useful adjunct to traditional face-to-face interviewing. Ultimately, electronic patient-generated data could produce automated red flags directed to the most appropriate clinicians (e.g., nurse, pain specialist, social worker, nutritionist) for further evaluation. Such system enhancement could greatly facilitate oncology nurses coordination role in caring for complex patients with cancer.

The Personal Patient Profile-Prostate decision support for men with localized prostate cancer: A multi-center randomized trial ☆

OBJECTIVE The purpose of this trial was to compare usual patient education plus the Internet-based Personal Patient Profile-Prostate, vs. usual education alone, on conflict associated with decision making, plus explore time-to-treatment, and treatment choice. METHODS A randomized, multi-center clinical trial was conducted with measures at baseline, 1-, and 6 months. Men with newly diagnosed localized prostate cancer (CaP) who sought consultation at urology, radiation oncology, or multi-disciplinary clinics in 4 geographically-distinct American cities were recruited. Intervention group participants used the Personal Patient Profile-Prostate, a decision support system comprised of customized text and video coaching regarding potential outcomes, influential factors, and communication with care providers. The primary outcome, patient-reported decisional conflict, was evaluated over time using generalized estimating equations to fit generalized linear models. Additional outcomes, time-to-treatment, treatment choice, and program acceptability/usefulness, were explored. RESULTS A total of 494 eligible men were randomized (266 intervention; 228 control). The intervention reduced adjusted decisional conflict over time compared with the control group, for the uncertainty score (estimate -3.61; (confidence interval, -7.01, 0.22), and values clarity (estimate -3.57; confidence interval (-5.85,-1.30). Borderline effect was seen for the total decisional conflict score (estimate -1.75; confidence interval (-3.61,0.11). Time-to-treatment was comparable between groups, while undecided men in the intervention group chose brachytherapy more often than in the control group. Acceptability and usefulness were highly rated. CONCLUSION The Personal Patient Profile-Prostate is the first intervention to significantly reduce decisional conflict in a multi-center trial of American men with newly diagnosed localized CaP. Our findings support efficacy of P3P for addressing decision uncertainty and facilitating patient selection of a CaP treatment that is consistent with the patient values and preferences.

Strength and balance training for adults with peripheral neuropathy and high risk of fall: current evidence and implications for future research

PURPOSE/OBJECTIVES To evaluate the evidence for strength- and balance-training programs in patients at high risk for falls, discuss how results of existing studies might guide clinical practice, and discuss directions for additional research. DATA SOURCES A search of PubMed and CINAHL® databases was conducted in June 2011 using the terms strength, balance training, falls, elderly, and neuropathy. Only clinical trials conducted using specific strength- or balance-training exercises that included community-dwelling adults and examined falls, fall risk, balance, and/or strength as outcome measures were included in this review. DATA SYNTHESIS One matched case-control study and two randomized, controlled studies evaluating strength and balance training in patients with diabetes-related peripheral neuropathy were identified. Eleven studies evaluating strength and balance programs in community-dwelling adults at high risk for falls were identified. CONCLUSIONS The findings from the reviewed studies provide substantial evidence to support the use of strength and balance training for older adults at risk for falls, and detail early evidence to support strength and balance training for individuals with peripheral neuropathy. IMPLICATIONS FOR NURSING The evidence demonstrates that strength and balance training is safe and effective at reducing falls and improving lower extremity strength and balance in adults aged 50 years and older at high risk for falls, including patients with diabetic peripheral neuropathy. Future studies should evaluate the effects of strength and balance training in patients with cancer, particularly individuals with chemotherapy-induced peripheral neuropathy.