The contribution of pain in determining the health status of cancer patients with bone metastases: A secondary analysis of data from three Phase III registration trials.

BACKGROUND: We aimed to provide a simple, descriptive health-status profile for cancer patients with bone metastases, based on the EuroQol EQ-5D, a tool commonly used to measure health utility scores, and to evaluate its association with the Brief Pain Inventory (BPI), a legacy pain-assessment tool. Although pain is one of five health-status dimensions measured by the EQ-5D, our understanding of how pain relates to the other EQ-5D dimensions is limited. METHODS: We derived data from 5500 patients with bone metastases who completed the EQ-5D and BPI. Regression analyses examined how BPI severity and interference scores correlated with EQ-5D utility scores and how BPI items associated with EQ-5D items, for the entire sample and by disease-type subgroup. RESULTS: Regardless of cancer site, the percentage of patients reporting moderate/severe problems in each of the five EQ-5D dimensions were pain/discomfort, 78%; usual activities, 58%; mobility, 55%; anxiety/depression, 57%; and self-care, 26%. BPI pain interference explained more of the variability in the EQ-5D utility scores than did pain severity (R2  = 41% vs. 34%). BPI worst pain, average pain, pain now, interference with general activity, and interference with work significantly predicted EQ-5D pain/discomfort, with odds ratio estimates <1. CONCLUSIONS: Pain/discomfort was the worst-rated dimension of the EQ-5D in this population, but the relationship of this item to BPI pain severity was modest, suggesting that the single pain item of the EQ-5D may be of limited utility in studies for which pain is an endpoint. SIGNIFICANCE: Health-status dimensions include more than pain. We examine the contribution of pain severity and pain-related functional interference in determining the health status of cancer patients with bone metastases. The pain dimension from a health-status measure may be an inadequate metric in clinical trials/clinical practice when pain is an important outcome.

Employment outcomes among survivors of common cancers: the Symptom Outcomes and Practice Patterns (SOAPP) study.

INTRODUCTION: Risk factors for employment difficulties after cancer diagnosis are incompletely understood, and interventions to improve post-cancer employment remain few. New targets for intervention are needed. METHODS: We assessed a cohort of 530 nonmetastatic cancer patients (aged ≤ 65 years, >6 months from diagnosis, off chemo- or radiotherapy) from the observational multi-site Symptom Outcomes and Practice Patterns study. Participants reported employment change, current employment, and symptoms. Groups were based on employment at survey (working full- or part-time versus not working) and whether there had been a change due to illness (yes versus no). The predictive power of symptom interference with work was evaluated for employment group (working stably versus no longer working). Race/ethnicity, gender, cancer type, therapy, and time since diagnosis were also assessed. Association between employment group and specific symptoms was examined. RESULTS: The cohort was largely non-Hispanic white (76 %), female (85 %), and diagnosed with breast cancer (75 %); 24 % reported a change in employment. On multivariable analysis, participants with at least moderate symptom interference were more likely to report no longer working than their less effected counterparts (odds ratio (OR) = 8.0, 95 % CI, 4.2-15.4), as were minority participants compared with their non-Hispanic white counterparts (OR = 3.2, 95 % CI, 1.8-5.6). Results from the multiple regression model indicated the combination of fatigue (OR = 2.3, 95 % CI, 1.1-4.7), distress (OR = 3.9, 95 % CI, 1.7-9.0), and dry mouth (OR = 2.6, 95 % CI, 1.1-6.2) together with race/ethnicity and time since diagnosis adequately accounted for employment group. CONCLUSIONS: Our findings support the hypothesis that residual symptom burden is related to post-cancer employment: Residual symptoms may be targets for intervention to improve work outcomes among cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: This analysis examines whether increased symptom burden is associated with a change to not working following a cancer diagnosis. We also examined individual symptoms to assess which symptoms were most strongly associated with not working after a cancer diagnosis. Our hope is that we will be able to use this information to both screen survivors post-active treatment as well as target high-risk symptoms for further and more aggressive intervention, in an attempt to improve post-cancer work outcomes.

Clinical benefit in patients with metastatic bone disease: results of a phase 3 study of denosumab versus zoledronic acid.

BACKGROUND: Patients with metastatic bone disease are living longer in the metastatic stage due to improvements in cancer therapy, making strategies to prevent the aggravation of bone disease and its complications, such as skeletal-related events (SREs) and pain, increasingly important. PATIENTS AND RESULTS: In this phase 3 trial in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma, denosumab reduced the risk of radiation to bone by 22% relative to zoledronic acid (P = 0.026), prevented worsening of pain and pain interference (2-point increase in Brief Pain Inventory score; P < 0.05 versus zoledronic acid), and reduced the frequency of a shift from no/weak opioid analgesic use to strong opioids (P < 0.05 versus zoledronic acid at months 3-5). Denosumab delayed the time to moderate-to-severe pain compared with zoledronic acid in patients with mild or no pain at the baseline (P = 0.04), supporting early treatment. Health-related quality-of-life scores were similar in both groups. The number needed to treat to avoid one SRE for denosumab was 3 patient-years versus placebo and 10 patient-years versus zoledronic acid. CONCLUSION: The use of denosumab was associated with better prevention of the complications of metastatic bone disease secondary to solid tumors or multiple myeloma versus zoledronic acid.

Minimal clinically meaningful differences for the EORTC QLQ-C30 and EORTC QLQ-BN20 scales in brain cancer patients.

BACKGROUND: We aimed to determine the smallest changes in health-related quality of life (HRQoL) scores in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire core 30 and the Brain Cancer Module (QLQ-BN20), which could be considered as clinically meaningful in brain cancer patients. MATERIALS AND METHODS: World Health Organisation performance status (PS) and mini-mental state examination (MMSE) were used as clinical anchors appropriate to related subscales to determine the minimal clinically important differences (MCIDs) in HRQoL change scores (range 0-100) in the QLQ-C30 and QLQ-BN20. A threshold of 0.2 standard deviation (SD) (small effect) was used to exclude anchor-based MCID estimates considered too small to inform interpretation. RESULTS: Based on PS, our findings support the following integer estimates of the MCID for improvement and deterioration, respectively: physical (6, 9), role (14, 12), and cognitive functioning (8, 8); global health status (7, 4*), fatigue (12, 9), and motor dysfunction (4*, 5). Anchoring with MMSE, cognitive functioning MCID estimates for improvement and deterioration were (11, 2*) and for communication deficit were (9, 7). Estimates with asterisks were <0.2 SD and were excluded from our MCID range of 5-14. CONCLUSION: These estimates can help clinicians evaluate changes in HRQoL over time, assess the value of a health care intervention and can be useful in determining sample sizes in designing future clinical trials.

Symptom burden in patients undergoing autologous stem-cell transplantation.

Patients who undergo autologous peripheral blood stem cell (PBSC) transplantation experience multiple symptoms that adversely affect quality of life. We assessed symptoms during the acute phase of autologous PBSC transplantation to determine the severity of individual symptoms and to determine overall symptom profiles in 100 patients with multiple myeloma or non-Hodgkin's lymphoma. Study subjects completed the blood and marrow transplantation module of the M. D. Anderson Symptom Inventory before hospitalization, during conditioning, on day of transplantation, at nadir (the time of lowest white blood cell count) and on day 30 post-transplantation. Additional symptom, quality-of-life and medical status measures were collected. Symptom means were mild at baseline, intensified during conditioning, peaked at nadir and decreased by day 30. At nadir, the most severe symptoms for the entire patient sample were lack of appetite, fatigue, weakness, feeling sick, disturbed sleep, nausea and diarrhea. Cancer diagnosis was a significant predictor of changes in symptoms over time. The patterns of fatigue, pain, sleep disturbance and lack of appetite were significantly different for patients with multiple myeloma as compared with patients with non-Hodgkin's lymphoma.

Does an oral analgesic protocol improve pain control for patients with cancer? An intergroup study coordinated by the Eastern Cooperative Oncology Group.

BACKGROUND: Cancer pain is highly prevalent and commonly undertreated. This study was designed to determine whether dissemination of a clinical protocol for pain management would improve outcomes in community oncology practices. PATIENTS AND METHODS: A pain management protocol was developed based on accepted guidelines. After baseline assessment, oncology practices were randomly assigned to 'analgesic protocol' (AP) sites, where oncologists implemented the guidelines in a group of lung or prostate cancer patients, or to 'physician discretion' (PD) sites, where customary treatment was continued. Patients treated on protocol and a comparison group of patients with pain due to breast cancer or myeloma were monitored for change in pain using the Brief Pain Inventory, and for change in other symptoms or mood. RESULTS: The protocol terminated early because of poor accrual. We compared groups using proportions of patients who had no or mild pain at follow-up. Although measures of protocol adherence did not suggest the occurrence of major practice change, the proportion of lung or prostate cancer patients with no or mild pain increased significantly from baseline for those treated at AP sites compared with those treated at PD sites. There was no significant difference between the breast and myeloma patients treated at AP sites versus those treated at PD sites. CONCLUSION: A protocol for cancer pain management can improve pain control. Diffusion of these benefits to other patients was not confirmed. Given the small sample size, these findings require confirmation in a larger trial.

Pain assessment: the advantages of using pain scales in lysosomal storage diseases.

UNLABELLED: Routine and standardized assessment of pain should be conducted in patients with conditions, such as Fabry disease, that are associated with chronic pain. Such pain assessments, using validated and reliable pain scales or questionnaires, should cover the severity, location, temporal pattern and quality of the pain and how the pain impacts on quality of life and normal daily activity. The severity or intensity of pain can be assessed on verbal descriptor scales, visual analogue scales and numerical rating scales, which rate pain on a scale from 'no pain' through to 'excruciating pain' or pain as bad as you can imagine'. Three pain questionnaires that include such rating scales are short enough to be used repeatedly in a clinical or research setting: the Memorial Pain Assessment Card, the McGill Pain Questionnaire and the Brief Pain Inventory (BPI). The BPI also measures the effect of pain on daily activity and quality of life, defines the location of pain and assesses the effectiveness of previous pain relief medication. CONCLUSIONS: Reliable instruments are available to assess pain in chronic disease. In Fabry disease, these should be used routinely to aid decisions concerning analgesic/pain control medication and to assess the effect of enzyme replacement therapy.

A fatigue clinic in a comprehensive cancer center: design and experiences.

Cancer-related fatigue is now the most prevalent symptom of cancer, occurring in 60-90% of patients. Fatigue has been identified by cancer patients as a factor influencing functionality and quality of life. Our objectives in developing a fatigue specialty clinic at The University of Texas M. D. Anderson Cancer Center were to improve our patients' quality of life by decreasing fatigue; educate health care providers, patients, and patients' families about cancer-related fatigue; develop an appropriate clinical and diagnostic evaluation for this symptom; correlate objective measures of fatigue with its clinical evaluation; and develop innovative treatment plans for cancer-related fatigue. This article describes the general clinic design and operations and the preliminary analysis of the first 40 patients evaluated in the fatigue clinic.

Fatigue during preoperative chemoradiation for resectable rectal cancer.

BACKGROUND: The aim of this study was to evaluate the severity and patterns of fatigue during preoperative chemoradiation therapy for locally advanced rectal cancer and determine whether there are predictors for patients who develop severe fatigue. METHODS: Seventy-two patients with resectable rectal cancer received chemoradiation (total radiation dose, 45 gray/25 fractions to the pelvis; continuous infusion of 5-fluorouracil [300 mg/m(2)]). The Brief Fatigue Inventory (BFI), a measure that categorizes fatigue severity on a 0-10 scale, was administered weekly during treatment. Severe fatigue was defined as 7-10 on the "worst level of fatigue" item. Demographics, disease information, toxicities, and blood counts were collected. Descriptive statistics, repeated measure analysis of variance, and multiple regression were used to examine fatigue and its correlates. RESULTS: Fatigue increased in 67% of patients during chemoradiation (CTX/XRT). The mean fatigue score increased from 3.16 before treatment to 4.62 at the end of treatment. A significant linear trend suggested that fatigue progressively got worse during CTX/XRT (F = 16.497, P < 0.001). However, 18% of patients experienced severe fatigue before CTX/XRT; this was predicted by uncontrolled pain (r(2) = 0.321; F = 16.52; P < 0.001). During CTX/XRT, uncontrolled diarrhea was the only predictor for increased fatigue (r(2) = 0.182; F = 7.77; P < 0.01). Approximately one-third of patients had severe fatigue, which impaired their function at the end of CTX/XRT. CONCLUSIONS: Preoperative chemoradiation therapy for patients with rectal cancer was associated with progressive fatigue during therapy. Based on identified predictors for fatigue, more active pain management before CXT/XRT and bowel management during CTX/XRT might reduce cancer-related fatigue in these patients.

A preliminary study of the utility of the brief hospice inventory.

The increasing number of palliative care patients necessitates a simple, reliable instrument to routinely measure outcomes among hospice patients. We tested the utility of the Brief Hospice Inventory (BHI) to assess outcomes of hospice patients and estimations of patients' outcomes by nurse caregivers. In a prospective study, 145 home-based hospice patients were enrolled in the study from VistaCare Hospice. During the first week of admission, patients and nurse caregivers completed the BHI, which assessed patients' symptoms, satisfaction with care, and quality of life. Factor analysis supported a two-factor structure for the BHI for patients and caregivers, including a symptom subscale and quality of life subscale. Patients with severe symptoms showed improvement on the symptom subscale, but not the quality of life subscale, during the first 2 weeks after admission. The BHI shows utility in measuring hospice patients' symptom severity and quality of life over time.

Clinical evaluation of once-weekly dosing of epoetin alfa in chemotherapy patients: improvements in hemoglobin and quality of life are similar to three-times-weekly dosing.

PURPOSE: To prospectively evaluate the effectiveness, safety, and clinical benefits of once-weekly epoetin alfa therapy as an adjunct to chemotherapy in anemic cancer patients. PATIENTS AND METHODS: A total of 3,012 patients with nonmyeloid malignancies who received chemotherapy were enrolled onto this multicenter, open-label, nonrandomized study conducted in 600 United States community-based practices. Patients received epoetin alfa 40,000 U once weekly, which could be increased to 60,000 U once weekly after 4 weeks dependent on hemoglobin response. Treatment was continued for a maximum of 16 weeks. RESULTS: Among the 2,964 patients assessable for efficacy, epoetin alfa therapy resulted in significant increases in hemoglobin levels, decreases in transfusion requirements, and improvements in functional status and fatigue as assessed by the linear analog scale assessment (energy level, ability to perform daily activities, and overall quality of life) and the anemia subscale of the Functional Assessment of Cancer Therapy-Anemia questionnaire. Improvements in quality-of-life parameters correlated significantly (P <.001) with increased hemoglobin levels. The direct relationship between hemoglobin and quality-of-life improvement was sustained during the 16-week study period, which is similar to findings of large community-based trials of three-times-weekly dosing. Once-weekly epoetin alfa was well tolerated, with most adverse events attributed to the underlying disease or concomitant chemotherapy. CONCLUSION: The results from this large, prospective, community-based trial suggest that once-weekly epoetin alfa therapy increases hemoglobin levels, decreases transfusion requirements, and improves quality of life in patients with cancer and anemia who undergo concomitant chemotherapy. Based on the results of this study, the clinical benefits and the adverse event profile of once-weekly epoetin alfa therapy in community-based practice are similar to those observed in the historical experience with the three-times-weekly dosage schedule.

Cancer pain: progress since the WHO guidelines.

In has been 15 years since the WHO Guidelines for the management of cancer pain were developed. This article reviews the guideline development and its effectiveness. Current trends in cancer care utilizing aggressive chemotherapeutic and surgical protocols lead to many patients living longer with advanced cancer and an attendant increase in pain. Future trends in cancer pain care are outlined.

Special aspects of cancer pain management in a Chinese general hospital.

China is still faced with a challenge in cancer pain management. The purposes of this study are to assess the current status of cancer pain management, and physicians' attitudes in China towards cancer pain management. The survey was done in a Chinese general hospital; 427 physicians and 387 cancer pain patients participated. The survey consisted of questionnaires to evaluate cancer pain management and physicians' knowledge of, and attitudes towards, cancer pain management. A total of 43% of patients with cancer pain and 51% with bone pain felt that they had been inadequately treated. The physicians rated the main reason for not using opioid drugs as the strong and difficult to control side-effects. The four main barriers to optimal management of cancer pain were: inadequate pain assessment; excessive state regulation of the prescribing of opioids; inadequate staff knowledge of pain management; and lack of access to powerful analgesics. To conclude: In China, there are some special aspects of cancer pain management, including physicians' concern about using opioid drugs, fear of being unable to manage adverse effects of opioids, and inadequately treated bone pain.

Cancer-related symptoms.

Patients with cancer experience multiple symptoms including pain, dyspnea, fatigue, depression, and cognitive impairment. These symptoms impair patients' daily functioning and their quality of life. Symptoms that can be well managed are often undertreated. A major barrier to adequate symptom treatment is poor assessment. The use of simple measurement scales greatly improves the symptom assessment process, helps direct treatment choices, and provides information about the effectiveness of treatment. Recently, better methods for symptom assessment have been developed, including brief self-report tools for the assessment of multiple symptoms and interactive voice response systems for assessing symptoms at home. Symptom assessment can be linked to evidence-based or best practice guidelines to expedite optimal symptom treatment. Because patients with cancer receiving radiotherapy are seen in the clinic frequently, the radiation oncologist can play an integral role in a comprehensive approach that involves both the medical and radiotherapeutic treatment of cancer-related symptoms.

Assessing symptom distress in cancer patients: the M.D. Anderson Symptom Inventory.

BACKGROUND: The purpose of this project was to develop the M. D. Anderson Symptom Inventory (MDASI), a brief measure of the severity and impact of cancer-related symptoms. METHODS: A list of symptoms was generated from symptom inventories and by panels of clinicians. Twenty-six symptoms and 6 interference items were rated by a validation sample of 527 outpatients, a sample of 30 inpatients from the blood and bone marrow transplantation service, and a cross-validation sample of 113 outpatients. Clinical judgment and statistical techniques were used to reduce the number of symptoms. Reliability, validity, and sensitivity of the MDASI were examined. RESULTS: Cluster analysis, best subset analysis, and clinical judgment reduced the number of symptoms to a "core" list of 13 that accounted for 64% of the variance in symptom distress. Factor analysis demonstrated a similar pattern in both outpatient samples, and two symptom factors and the interference scale were reliable. Expected differences in symptom pattern and severity were found between patients with "good" versus "poor" performance status and between patients in active therapy and patients who were seen for follow-up. Patients rated fatigue-related symptoms as the most severe. Groups of patients classified by disease or treatment had severe symptoms that were not on the "core" list. CONCLUSIONS: The core items of the MDASI accounted for the majority of symptom distress reported by cancer patients in active treatment and those who were followed after treatment. The MDASI should prove useful for symptom surveys, clinical trials, and patient monitoring, and its format should allow Internet or telephone administration.

Minority cancer patients and their providers: pain management attitudes and practice.

BACKGROUND: The goals of the current studies were: 1) to determine the pain treatment needs of socioeconomically disadvantaged African-American and Hispanic patients with recurrent or metastatic cancer and 2) to assess the attitudes of health care professionals who treat them. METHODS: In the first study 108 African-American and Hispanic patients with metastatic or recurrent cancer and pain completed a survey about their pain intensity, pain interference, and attitudes toward analgesic medications. Physicians also rated their patients' pain and the adequacy of the patients' current analgesic prescriptions was assessed. In the second study 55 physicians and nurses who treat these patients completed a questionnaire regarding cancer pain and its management in their practice settings. RESULTS: Approximately 28% of the Hispanic and 31% of the African-American patients received analgesics of insufficient strength to manage their pain. Although the majority of patients received appropriate analgesics, 65% reported severe pain. Physicians underestimated pain severity for 64% of the Hispanic and 74% of the African-American patients. Physicians were more likely to underestimate the pain severity of female patients than male patients. Inadequate pain assessment, patient reluctance to report pain, and lack of staff time were perceived as barriers to pain management. CONCLUSIONS: Although the data suggest recent improvements in analgesic prescribing practices for African-American and Hispanic cancer patients, the majority of patients reported high levels of pain and limited pain relief from analgesic medications. Inadequate pain assessment remains a major barrier to optimal cancer pain treatment.

Cancer pain management by radiotherapists: a survey of radiation therapy oncology group physicians.

PURPOSE: Radiation Therapy Oncology Group (RTOG) physicians were surveyed to determine their approach to and attitudes toward cancer pain management. METHODS AND MATERIALS: Physicians completed a questionnaire assessing their estimates of the magnitude of pain as a specific problem for cancer patients, their perceptions of the adequacy of pain management, and their report of how they manage pain in their own practice setting. RESULTS: Eighty-three percent believed the majority of cancer patients with pain were undermedicated. Forty percent reported that pain relief in their own practice setting was poor or fair. Assessing a case scenario, 23% would wait until the patient's prognosis was 6 months or less before starting maximal analgesia. Adjuvants and prophylactic side effect management were underutilized in the treatment plan. Barriers to pain management included poor pain assessment (77%), patient reluctance to report pain (60%), patient reluctance to take analgesics (72%), and staff reluctance to prescribe opioids (41%). CONCLUSIONS: Physicians' perceptions of barriers to cancer pain management remain quite stable over time, and physicians continue to report inadequate pain treatment education. Future educational efforts should target radiation oncologists as an important resource for the treatment of cancer pain.

Validation of the Brief Pain Inventory in a Taiwanese population.

Assessment of pain in cancer patients is very important to all health care professionals. This paper describes the development of a Taiwanese version of the Brief Pain Inventory (BPI-T) and discusses its psychometric properties in Taiwan. The BPI-T was developed from the original BPI using back-translation and committee review. A total of 534 cytologically or pathologically diagnosed cancer patients in three medical centers in Taiwan were interviewed between July 1992 and October 1997. The intraclass correlation coefficient for the test-retest reliability was 0.79 for the pain severity scale and 0.81 for the pain interference scale. The explained variance for the within-scale factor analyses was larger than 60% in both scales. The coefficient alpha for the internal reliability was 0.81 for the severity scale and 0.89 for the interference scale. Confirmatory factor analysis of the BPI-T clearly identified the same two scales (severity and interference scales) in the 299 adult patients (age between 20-64) with high education (education years > 9) or patients at an early stage of disease. However, in the 235 nonadult patients with distant metastasis or low education patients with distant metastasis, the "most severe pain" item loaded more to the interference scale than the severity scale. Convergent validity of the pain severity was demonstrated by significant correlations with stage of disease (National Cancer Institute's Surveillance, Epidemiology, and End Results Program [SEER]), performance status (Eastern Cooperative Oncology Group [ECOG]), and pain interference. In conclusion, interviewer-administered BPI-T was a reliable instrument for cancer pain severity and its interference in Taiwan. Additionally, it was a valid instrument on adult cancer patients with high education or patients at an early stage of disease.

The effects of pain severity on health-related quality of life: a study of Chinese cancer patients.

BACKGROUND: The health-related functioning of patients with cancer is compromised by several factors, including the disease process, treatment, and the various symptoms that are produced by both disease and treatment. This study was designed to specify the relationship between patients' pain severity and their self-reported quality of life. METHODS: The study enrolled 216 consecutive consenting adult patients from 2 Chinese cancer centers with pathologically-diagnosed metastatic cancer who could understand and complete the self-report measures. The majority had cancer-related pain and were receiving analgesics. The Chinese version of the Brief Pain Inventory was used to assess the severity and interference of pain. A Chinese translation of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) was used to assess health-related functional status. Patients' physicians completed a form that indicated characteristics of the patients' cancer, Eastern Cooperative Oncology Group performance status, pain, and current pain treatment. RESULTS: Increasing severity of pain was associated with worsening health-related functioning, even when an estimate of disease severity was taken into account. The correlation between pain severity and impairment was nonlinear. The functional health and well-being of cancer patients with no or mild pain was significantly less impaired than that of patients with moderate or severe pain. The impairment of patients with moderate and severe pain did not differ. CONCLUSIONS: Pain severity is an important variable to be taken into account when quality of life outcome measures are considered. The functioning of cancer patients with well-controlled (mild) pain did not differ significantly from that of patients without pain. Providing pain relief should significantly improve the functional status of cancer patients.