Validation and real-world assessment of the Functional Assessment of Anorexia-Cachexia Therapy (FAACT) scale in patients with advanced non-small cell lung cancer and the cancer anorexia-cachexia syndrome (CACS).

PURPOSE: Patients with cancer anorexia-cachexia syndrome (CACS) suffer a significant symptom burden, impaired quality of life (QoL), and shorter survival. Measurement of QoL impairments related to CACS is thereby important both in clinical practice and in research. We aimed to further validate the Functional Assessment of Anorexia-Cachexia Therapy (FAACT) scale in an advanced lung cancer population. METHODS: We tested the performance of the FAACT and its anorexia-cachexia subscale (ACS) within a dataset of patients with advanced non-small cell lung cancer (aNSCLC), using standard statistical methods. We then compared the performance of commonly used QoL measures stratified by CACS status and by patient self-report of appetite and weight loss. RESULTS: The FAACT and its ACS demonstrate internal validity consistent with acceptable published ranges for other QoL scales (Cronbach alpha = 0.9 and 0.79, respectively). Correlation coefficients demonstrate moderate correlations in the expected directions between FAACT and ACS and scales that measure related constructs. Comparing patients with and without CACS, the ACS is more sensitive to change than other QoL instruments (mean score 33.1 vs. 37.2, p = 0.011, ES = 0.58). CONCLUSION: In patients with aNSCLC, the FAACT and its ACS performed well compared with other instruments, further supporting their validity and value in clinical research. FAACT and ACS scores covaried with symptoms and other QoL changes that are typical hallmarks of CACS, lending further support to their use as QoL endpoints in clinical trials among patients with CACS.

Time course of arthralgia among women initiating aromatase inhibitor therapy and a postmenopausal comparison group in a prospective cohort.

BACKGROUND: More than 80,000 postmenopausal breast cancer patients in the United States each year are estimated to begin a 5-year course of aromatase inhibitors (AIs) to prevent recurrence. AI-related arthralgia (joint pain and/or stiffness) may contribute to nonadherence, but longitudinal data are needed on arthralgia risk factors, trajectories, and background in postmenopause. This study sought to describe 1-year arthralgia trajectories and baseline covariates among patients with AI and a postmenopausal comparison group. METHODS: Patients initiating AIs (n = 91) were surveyed at the time of AI initiation and at 6 repeated assessments over 1 year. A comparison group of postmenopausal women without breast cancer (n = 177) completed concomitantly timed surveys. Numeric rating scales (0-10) were used to measure pain in 8 joint pair groups (bilateral fingers, wrists, elbows, shoulders, hips, knees, ankles, and toes). Poisson regression models were used to analyze arthralgia trajectories and risk factors. RESULTS: By week 6, the AI-initiating group had more severe arthralgia than did the comparison group (ratio of means = 1.8, 95% confidence interval = 1.24-2.7, P = .002), adjusting for baseline characteristics. Arthralgia then worsened further over 1 year in the AI group. Menopausal symptom severity and existing joint-related comorbidity at baseline among women initiating AI were associated with more severe arthralgia over time. CONCLUSIONS: Patients initiating AI should be told about the timing of arthralgia over the first year of therapy, and advised that it does not appear to resolve over the course of a year. Menopausal symptoms and joint-related comorbidity at AI initiation can help identify patients at risk for developing AI-related arthralgia.

Monitoring population health for Healthy People 2020: evaluation of the NIH PROMIS® Global Health, CDC Healthy Days, and satisfaction with life instruments.

PURPOSE: Healthy People 2020 identified health-related quality of life and well-being (WB) as indicators of population health for the next decade. This study examined the measurement properties of the NIH PROMIS(®) Global Health Scale, the CDC Healthy Days items, and associations with the Satisfaction with Life Scale. METHODS: A total of 4,184 adults completed the Porter Novelli's HealthStyles mailed survey. Physical and mental health (9 items from PROMIS Global Scale and 3 items from CDC Healthy days measure), and 4 WB factor items were tested for measurement equivalence using multiple-group confirmatory factor analysis. RESULTS: The CDC items accounted for similar variance as the PROMIS items on physical and mental health factors; both factors were moderately correlated with WB. Measurement invariance was supported across gender and age; the magnitude of some factor loadings differed between those with and without a chronic medical condition. CONCLUSIONS: The PROMIS, CDC, and WB items all performed well. The PROMIS items captured a broad range of functioning across the entire continuum of physical and mental health, while the CDC items appear appropriate for assessing burden of disease for chronic conditions and are brief and easily interpretable. All three measures under study appear to be appropriate measures for monitoring several aspects of the Healthy People 2020 goals and objectives.

Improving health-related quality of life in non-small-cell lung cancer with current treatment options.

Non-small-cell lung cancer (NSCLC) accounts for > 80% of all lung carcinomas, with the majority of patients presenting with late-stage disease. Selection of an appropriate therapy depends on the stage of disease, with treatment of patients with advanced NSCLC often aimed at palliation of symptoms and improving the well-being of patients. Health-related quality of life (QOL) has been largely ignored as an endpoint in clinical trials for NSCLC, but there is increasing acceptance by clinicians and regulatory authorities that alleviation of symptoms and improved health-related QOL should be carefully considered. This article discusses current approaches to measuring health-related QOL. This discussion is followed by a brief review of some of the current treatment options for patients with NSCLC and their effect on health-related QOL.

Long-term health-related quality of life, growth, and spiritual well-being after hematopoietic stem-cell transplantation.

PURPOSE: To examine health-related quality of life (HRQOL) and growth, and spiritual well-being in adult survivors of hematopoietic stem-cell transplantation (HSCT) for a malignant disease. METHODS: HSCT survivors (n = 662) were recruited through the International Bone Marrow Transplant Registry/Autologous Blood and Marrow Transplant Registry and were drawn from 40 transplantation centers. HSCT survivors completed a telephone interview and a set of questionnaires a mean of 7.0 years post-HSCT (range, 1.8 to 22.6 years). Study measures included a variety of standardized measures of HRQOL and growth and spiritual well-being. An age- and sex-matched healthy comparison (HC) group (n = 158) was recruited using a peer nomination method. The HC group completed a parallel telephone interview and set of questionnaires. RESULTS: Multivariate analysis of variance analyses found the HSCT survivor group reported poorer status relative to the HC group for all HRQOL outcome clusters including physical health, physical functioning, social functioning, psychological adjustment, and dyadic adjustment. In contrast, the HSCT survivor group reported more psychological and interpersonal growth. Mean effect size for the 24 outcome indices examined was 0.36 standard deviations, an effect size often considered clinically meaningful or important. The largest group differences were found for measures of general health, physical function and well-being, depression, cognitive function, and fatigue. CONCLUSION: The experience of HSCT for a malignant disease has a wide-ranging, longstanding, and profound impact on adult recipients. Relative to healthy controls, HSCT survivors reported poorer physical, psychological, and social functioning but, conversely, more psychological and interpersonal growth, differences that appeared to persist many years after HSCT.

Limited access trial using amifostine for protection against cisplatin- and three-hour paclitaxel-induced neurotoxicity: a phase II study of the Gynecologic Oncology Group.

PURPOSE: The purpose of this study was to determine whether amifostine (WR-2721) prevents or ameliorates clinically significant (grade 2 to 4) neurotoxicity associated with cisplatin and 3-hour paclitaxel chemotherapy. MATERIALS AND METHODS: The chemotherapy program consisted of intravenous paclitaxel 175 mg/m2 over 3 hours followed by amifostine 740 mg/m2 and cisplatin 75 mg/m2 administered over 90 minutes beginning 15 minutes after amifostine administration. At baseline, before each treatment cycle, and for 3 months after completing chemotherapy, patients were evaluated for evidence of neurotoxicity and other treatment-related adverse effects using three methods: standard clinical evaluation (National Cancer Institute common toxicity criteria [CTC] grading), a neurotoxicity questionnaire to assess symptoms and limitations imposed by peripheral neuropathy, and vibration perception threshold (VPT) testing. RESULTS: Four of 27 assessable patients developed grade 2 to 4 neurotoxicity based on clinical assessments and CTC grading. This number of neuropathic events exceeded the predetermined threshold level for a second stage of accrual and the study was closed. CONCLUSION: Amifostine's level of activity in this trial was insufficient to warrant further study in a phase III trial. Based on the receiver operating characteristic analysis, it would appear that VPT measurements are less sensitive to the development of peripheral neuropathy than the neurotoxicity questionnaire. The questionnaire, referred to as the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity, may be used instead of VPT measurements in future studies of chemotherapy-induced peripheral neuropathy.

Correlation between the international consensus definition of the Cancer Anorexia-Cachexia Syndrome (CACS) and patient-centered outcomes in advanced non-small cell lung cancer.

CONTEXT: The cancer anorexia-cachexia syndrome (CACS) is common in patients with advanced solid tumors and is associated with adverse outcomes including poor quality of life (QOL), impaired functioning, and shortened survival. OBJECTIVES: To apply the recently posed weight-based international consensus CACS definition to a population of patients with advanced non-small cell lung cancer (NSCLC) and explore its impact on patient-reported outcomes. METHODS: Ninety-nine patients participated in up to four study visits over a six-month period. Longitudinal assessments included measures of physical function, QOL, and other clinical variables such as weight and survival. RESULTS: Patients meeting the consensus CACS criteria at Visit 1 had a significantly shorter median survival (239.5 vs. 446 days; hazard ratio, 2.06, P < 0.05). Physical function was worse in the CACS group (mean Karnofsky Performance Status score 68 vs. 77, Eastern Cooperative Oncology Group Performance Status score 1.8 vs. 1.3, P < 0.05 for both), as was QOL (Functional Assessment of Cancer Therapy-General [FACT-G] Lung Cancer subscale of 17.2 vs. 19.9, Anorexia/Cachexia subscale of 31.4 vs. 37.9, P < 0.05 for both). Differences in the FACT-G and the Functional Assessment of Chronic Illness Therapy-Fatigue subscale approached but did not reach statistical significance. Longitudinally, all measures of physical function and QOL worsened regardless of CACS status, but the rate of decline was more rapid in the CACS group. CONCLUSION: The weight-based component of the recently proposed international consensus CACS definition is useful in identifying patients with advanced NSCLC who are likely to have significantly inferior survival and who will develop more precipitous declines in physical function and QOL. This definition may be useful for clinical screening purposes and identify patients with high palliative care needs.

Meta-analysis provides evidence-based effect sizes for a cancer-specific quality-of-life questionnaire, the FACT-G.

OBJECTIVE: To compare Cohen's guidelines for small (0.2), medium (0.5), and large (0.8) effect sizes with empirical estimates for a cancer-specific health-related quality-of-life questionnaire (HRQOL), the Functional Assessment of Cancer Therapy - General (FACT-G). METHODS: Seventy-one papers satisfied inclusion criteria for meta-analysis. Blinded to the HRQOL results, three "experts" (with expertise in interpreting the FACT-G questionnaire and managing cancer patients), predicted the relative magnitude of HRQOL mean differences. Size classes (small, medium, large) were defined in terms of relevance to clinical decision making. The experts worked independently and based their predictions on patient characteristics and clinical circumstances. Their judgments were linked with FACT-G results and inverse-variance-weighted mean effect sizes calculated for each size class. RESULTS: At least two experts were perfectly concordant and up to one was discordant by at most one size category for 833 of the mean differences; for these, weighted kappas were generally in the "substantial" range (0.60-0.79). Of these mean differences, 617 were cross-sectional; small, medium, and large mean effect sizes were physical well-being 0.42, 0.87, 1.6; functional well-being 0.37, 0.71, 1.6; emotional well-being 0.32, 0.40, no large differences; and social well-being 0.14, 0.23, no large differences. Two hundred and sixteen longitudinal mean differences yielded small and medium effect sizes: physical well-being 0.26, 0.34; functional well-being 0.14, 0.28; emotional well-being 0.27, 0.23; and social well-being 0.08, 0.01. There was virtually no evidence for large longitudinal effects. CONCLUSION: These results provide specific, evidence-based alternatives to Cohen's generic guidelines, for use in sample-size calculations for the FACT-G and interpretation of the clinical significance of effects measured with FACT-G.

Use of epoetin and darbepoetin in patients with cancer: 2007 American Society of Hematology/American Society of Clinical Oncology clinical practice guideline update.

PURPOSE: To update the American Society of Clinical Oncology/American Society of Hematology (ASCO/ASH) recommendations for the use of epoetin. The guideline was expanded to address use of darbepoetin and thromboembolic risk associated with these agents. METHOD: An Update Committee ("Committee") reviewed and analyzed data published since 2002 through July 2007. MEDLINE and the Cochrane Collaboration Library databases were searched. RECOMMENDATIONS: For patients with chemotherapy-associated anemia, the Committee continues to recommend initiating an erythropoiesis-stimulating agent (ESA) as hemoglobin (Hb) approaches, or falls below, 10 g/dL, to increase Hb and decrease transfusions. ESA treatment continues to be recommended for patients with low-risk myelodysplasia for similar reasons. There is no evidence showing increased survival as a result of ESA treatment. Conclusive evidence is lacking that, absent clinical circumstances necessitating earlier treatment, initiating ESAs at Hb levels greater than 10 g/dL either spares more patients from transfusion or substantially improves their quality of life. Starting doses and dose modifications based on response or lack thereof should follow the package insert. Continuing ESAs beyond 6 to 8 weeks in the absence of response, assuming appropriate dose increase has been attempted in nonresponders as per US Food and Drug Administration-approved label, does not seem to be beneficial, and ESA therapy should be discontinued. The Committee recommends monitoring iron stores and supplementing iron intake for ESA-treated patients. ESAs should be used cautiously with chemotherapy, or in clinical states, associated with elevated risk for thromo-embolic complications. The Committee also cautions against ESA use for patients with cancer who are not receiving chemotherapy, since recent trials report increased thromboembolic risks and decreased survival under these circumstances.

Use of epoetin and darbepoetin in patients with cancer: 2007 American Society of Clinical Oncology/American Society of Hematology clinical practice guideline update.

PURPOSE: To update the American Society of Clinical Oncology/American Society of Hematology (ASCO/ASH) recommendations for the use of epoetin. The guideline was expanded to address use of darbepoetin and thromboembolic risk associated with these agents. METHOD: An Update Committee ("Committee") reviewed and analyzed data published since 2002 through July 2007. MEDLINE and the Cochrane Collaboration Library databases were searched. RECOMMENDATIONS: For patients with chemotherapy-associated anemia, the Committee continues to recommend initiating an erythropoiesis-stimulating agent (ESA) as hemoglobin (Hb) approaches, or falls below, 10 g/dL, to increase Hb and decrease transfusions. ESA treatment continues to be recommended for patients with low-risk myelodysplasia for similar reasons. There is no evidence showing increased survival as a result of ESA treatment. Conclusive evidence is lacking that, absent clinical circumstances necessitating earlier treatment, initiating ESAs at Hb levels greater than 10 g/dL either spares more patients from transfusion or substantially improves their quality of life. Starting doses and dose modifications based on response or lack thereof should follow the package insert. Continuing ESAs beyond 6 to 8 weeks in the absence of response, assuming appropriate dose increase has been attempted in nonresponders as per US Food and Drug Administration-approved labeling, does not seem to be beneficial, and ESA therapy should be discontinued. The Committee recommends monitoring iron stores and supplementing iron intake for ESA-treated patients. ESAs should be used cautiously with chemotherapy, or in clinical states, associated with elevated risk for thromboembolic complications. The Committee also cautions against ESA use for patients with cancer who are not receiving chemotherapy, since recent trials report increased thromboembolic risks and decreased survival under these circumstances.