Predictors of Quality of Life in Oncology Outpatients with Pain from Bone Metastasis

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1 234 Journal of Pain and Symptom Management Vol. 30 No. 3 September 2005 Original Article Predictors of Quality of Life in Oncology Outpatients with Pain from Bone Metastasis Tone Rustøen, RN, PhD, Torbjørn Moum, PhD, Geraldine Padilla, PhD, Steven Paul, PhD, and Christine Miaskowski, RN, PhD Faculty of Nursing (T.R.), Oslo University College, Oslo, Norway; Department of Behavioral Sciences in Medicine (T.M.), University of Oslo, Oslo, Norway, and Department of Physiological Nursing (T.R. G.P., S.P., C.M.), School of Nursing, University of California, San Francisco, California, USA Abstract The relationship between pain and quality of life (QOL) in cancer patients is complex due to the number and the diversity of factors that can influence pain and QOL. The aims of this study of oncology outpatients with pain from bone metastasis were: 1) to determine the extent to which pain characteristics (i.e., severity, duration, meaning of pain, and perceived availability and efficacy of pain relief), psychological distress (i.e., depression), physical functioning, social functioning and QOL are intercorrelated, and 2) to determine which of these variables are important predictors of QOL. A total of 157 oncology outpatients completed questionnaires that evaluated pain, QOL, depression, physical functioning, and social functioning at the time of enrollment into a randomized clinical trial that evaluated the effectiveness of a psychoeducational intervention to improve cancer pain management. Pearson product moment correlation coefficients were calculated to examine the relationships among the study variables. A blockwise, hierarchical multiple regression analysis was performed to determine which variables were the most important predictors of QOL. Meaning of pain was significantly correlated with all the other variables, in particular pain intensity and duration. The most important factors that predicted QOL were depression, social functioning, and physical functioning. Depression proved to be the most important predictor of QOL. J Pain Symptom Manage 2005;30: Ó 2005 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. Key Words Cancer pain, quality of life, oncology outpatients, bone metastasis, depression, physical function, social function Introduction Quality of life (QOL) has been defined as a person s sense of well-being that stems from satisfaction or dissatisfaction with the areas of life that are important to him/her. 1 QOL is Address reprint requests to: Tone Rustøen, RN, PhD, Faculty of Nursing, Oslo University College, Postbox 4, St. Olav s Place, 0130 Oslo, Norway. Accepted for publication: April 5, Ó 2005 U.S. Cancer Pain Relief Committee Published by Elsevier Inc. All rights reserved. often viewed as a multidimensional construct that encompasses several domains (e.g., health, physical functioning, psychological status, spiritual well-being, social functioning). Although several studies have documented that unrelieved cancer pain can have negative effects on QOL, 2--8 it is not clear at the present time exactly which pain characteristics and patient characteristics interact to influence the QOL of patients who are experiencing cancer pain /05/$--see front matter doi: /j.jpainsymman

2 Vol. 30 No. 3 September 2005 Predictors of QOL 235 Table 1 Portenoy s Hypotheses About the Relationships Between Cancer Pain and Quality of Life 1. Pain intensity is related to the degree of nociception, but nociception alone cannot account for the presence or the intensity of pain. 2. The level of psychological distress associated with pain (i.e., anxiety, depression, or both) is distinct from the report of pain intensity. 3. Perceived pain chronicity is probably a critical factor that influences the distress associated with pain. 4. The meaning of the pain to the patient may influence pain intensity and/or psychological distress attributable to the pain. 5. Pain intensity and psychological distress attributable to the pain are strongly influenced by the perceived availability and efficacy of pain treatments. 6. The severity, chronicity, and meaning of pain; the perceived availability of pain relief; and the degree of psychological distress associated with pain are all related to QOL. 7. All of these concepts can change rapidly and they may vary together or independently. 8. In some patients, specific intervening variables (e.g., impaired physical functioning) can be identified that appear to provide a link between pain and QOL. 9. Pain intensity, the psychological distress attributable to pain, and overall QOL are influenced by availability and behavior of significant others. QOL 5 quality of life. Adapted from Portenoy. 9 A Conceptual Model of the Relationships Between Cancer Pain and QOL In a review article written 15 years ago, Portenoy 9 hypothesized about the relationships between cancer pain and QOL. These hypotheses are summarized in Table 1 and a conceptualization of how these concepts may be interrelated is illustrated in Figure 1. First, Portenoy emphasized that while the intensity of pain is related to the degree of tissue damage, tissue damage alone cannot explain the presence or the intensity of cancer pain. Among other things, psychological distress (e.g., anxiety and depression) can affect pain intensity. Yet, at the same time, pain intensity alone cannot account for an individual s level of distress. In addition, while both pain intensity and psychological distress associated with pain can have a negative effect on QOL, 2--8 neither fully accounts for all of the changes in QOL associated with cancer pain. In his review, Portenoy 9 noted that both the level of psychological distress attributable to cancer pain and the overall suffering experienced by patients appear to be related to the perceived chronicity of the pain (i.e., how long the patients believe the pain will last and how long the patients were in pain). In addition, important variables, such as reduced physical functioning, may influence the relationships between cancer pain and QOL. Portenoy noted that all of these factors can change quickly and that they can vary together or independently from each other. The meaning of the pain to the patient (e.g., the perception or belief that the cancer is progressing) also may affect the intensity of the pain, the psychological distress associated Perceived pain chronicity (How long have you been in pain?) Availability and behavior of significant others (Social functioning from SF-36) Degree of nociception (Bone metastasis) Pain intensity (Current pain at its worst) Psychological distress (Depression from POMS) Quality of life (How good is your quality of life? from MQOLS-CA2) Meaning of pain to patient (How upsetting is your pain to you? from PES) Perceived availability & efficacy of pain relief (In the last week, how much pain relief have you gotten from your pain medicine?) Intervening variables (Physical functioning from KPS) Fig. 1. Hypothesized relationships among pain characteristics and quality of life.

3 236 Rustøen et al. Vol. 30 No. 3 September 2005 with the pain, or the individual s QOL. According to Portenoy s model, 9 additional factors that can influence the relationships among cancer pain, psychological distress, and QOL include the availability and efficacy of pain treatments, as well as the perceived availability and specific behaviors of significant others. The review of the literature that follows focuses on studies that have examined some of the hypotheses listed in Table 1. Review of the Literature Pain Characteristics and QOL. Rummans and colleagues 4 found that, in patients with recurrent breast and gynecologic cancer, pain frequency, intensity, and interference with activities correlated more strongly with the physical and social domains of QOL than with the psychological or spiritual domains. Strang and Qvarner 5 found a positive correlation between pain intensity and anxiety and depression in cancer patients. Anxiety and depression were significantly worse in cancer patients with no or almost no pain-free periods. Psychosocial Well-Being and QOL. When developing an instrument to measure QOL in patients with cancer pain, Padilla and colleagues 10 identified psychological well-being and interpersonal well-being as important QOL domains. The importance of these domains is substantiated by studies that showed that oncology outpatients with cancer pain reported significantly higher depression, anxiety, and total mood disturbance scores (as measured by the Profile of Mood States 11 ) compared to pain-free patients. 3,7 In addition, unrelieved cancer pain had a negative impact on social activities. 5 Physical Functioning and Pain. Several studies have examined the relationships between cancer pain and physical functioning. 5,7,10 In one study, 7 oncology outpatients with somatic and visceral pain had significantly lower physical functioning scores than pain-free cancer patients. Padilla and colleagues 10 found that physical well-being (including general functioning and disease/treatmentspecific attributes) was one of the most important domains of QOL for cancer patients. In addition, unrelieved pain was found to have a negative impact on activities of daily living and physical functioning in a sample of oncology outpatients. 5 Relationships Between Pain and Other Independent Variables. In men with prostate cancer, 6 pain was a significant predictor of decreased QOL together with older age, lower ratings of health care availability, and the need for palliative treatment. In another study, 8 females reported higher rates of post-treatment pain than men. In a large study on Norwegian cancer patients, 12 sex, age, level of education, and co-habitation were not related to pain, but employment status was. Patients who were on disability pensions had significantly more pain than patients who were employed or were attending school. As noted in the Oncology Nursing Society s position paper on cancer pain, 13 little is known about the true impact of pain on the individual diagnosed with cancer. While the studies discussed above reveal the complexity of the relationships among various patient and pain characteristics and QOL in patients with cancer, no studies done to date have attempted to examine the relationships among all of the concepts elaborated in Portenoy s model 9 and their impact on QOL. Therefore, the overall purpose of this study was to test the relationships among various patient and pain characteristics identified in Portenoy s model 9 and their impact on QOL. The two specific research questions addressed in this study of oncology outpatients with pain from bone metastasis were: 1) to determine the extent to which pain characteristics (i.e., pain intensity, pain duration, meaning of pain, and pain relief), psychological distress (i.e., depression), physical functioning, social functioning and QOL are intercorrelated, and 2) to determine which of these variables are the most important predictors of QOL. Methods Sample and Settings Two hundred and twelve oncology outpatients who were experiencing pain from bone metastasis were recruited from seven outpatient settings in Northern California to participate in a randomized clinical trial (RCT) that

4 Vol. 30 No. 3 September 2005 Predictors of QOL 237 tested the effectiveness of a psychoeducational intervention to improve cancer pain management. The results of this trial are reported elsewhere. 14 Of the 212 patients enrolled in the RCT, 174 completed the trial. This study reports on findings from the baseline data that were collected prior to the intervention. Complete data for the regression analyses were provided by 157 patients. No differences were found in any of the study variables between the patients who did (n 5 157) and did not (n 5 55) provide complete baseline data. The study was approved by the Committee on Human Research at the University of California, San Francisco and at each of the study sites. The participants were adult oncology outpatients (O 18 years) who were able to read, write, and understand English. All participants had Karnofsky Performance Status (KPS) scores of $ 50, an average pain intensity scores of $ 2.5, and radiographic evidence of bone metastasis. In brief, patients were approached in the outpatient setting by a recruitment nurse who explained the study and obtained written informed consent. Baseline data were collected at the time of enrollment into the study. Measures Used for Variables in the Model Patients completed a variety of questionnaires and their medical records were reviewed for disease and treatment information. The measures that were used for each of the components of the model illustrated in Figure 1 are described below. QOL. Quality of life was measured using the Multidimensional Quality of Life Scale-Cancer (MQOLS-CA2). This instrument was developed and revised several times by Padilla and colleagues. 15,16 Because this QOL scale contained individual items related to social factors, physical factors, and depression (other independent variables in the study), one single item (i.e., How good is your quality of life? ) was used as the measure of QOL in these analyses. Single item ratings of QOL have been shown to be equally valid and reliable measures as total scores from a multidimensional instrument. 17,18 Patients rated this single item using a 0 (extremely poor QOL) to 10 (excellent QOL) scale. Degree of Nociception. Because all of the patients in this study had pain from bone metastasis this variable was not entered into the model. Pain Intensity. Worst pain intensity was measured using a 0 (no pain) to 10 (excruciating pain) numeric rating scale (NRS). NRS s are valid and reliable measures of pain intensity. 19,20 Worst pain was used in these analyses because it had more variance than pain right now or average pain. Perceived Pain Chronicity. Patients reported the length of time they were in pain by choosing one of six responses (i.e., less than one week, one to two weeks, about one month, two to six months, seven months to one year, or more than a year). This variable was entered into the analyses as a continuous variable. Perceived Availability and Efficacy of Pain Relief. This was measured using the pain relief scale from the Brief Pain Inventory (BPI). 21 Patients rated the relief they had gotten from their pain medicine in the past week using a 0% (no relief) to 100% (complete relief) scale. Meaning of Pain to the Patient. This was evaluated using a single item from the Pain Experience Scale (PES) developed by Ferrell and colleagues. 22 Patients were asked to make a mark on a 10-cm visual analogue scale that asked the question How upsetting is your pain to you? with the anchors that ranged from none to a great deal. Availability and Behavior of Significant Others. We measured this using the social functioning scale from the Medical Outcomes Study-Short Form (MOS-SF-36). 23 This scale consists of 2 items: To what extent has your physical health or emotional problems interfered with your normal social activities with family, friends, neighbors, or groups? and How much of the time has your physical health or emotional problems interfered with your social activities (like visiting with friends, relatives, etc.)? This scale is widely used and has established validity and reliability. 24 Psychological Distress. This was measured using the depression subscale of the Profile of Mood states (POMS). 25 The validity and reliability of

5 238 Rustøen et al. Vol. 30 No. 3 September 2005 the scale have been established. 26 Patients respond on a 5-point Likert scale ranging from 0 (no feeling) to 4 (extreme feelings) about their mood states during the last week including today. Intervening Variables. Physical functioning was the intervening variable tested in these analyses. Physical functioning was measured using the Karnofsky Performance Status (KPS) score. 27 The KPS used in this study was a patient self-report measure that consisted of a series of eight items for ranking functional status that ranged from 30 (disability with hospitalization needed) to 100 (adequate health status with no complaints or evidence of disease). Patients were asked to rate their level of physical functioning with respect to their abilities at the present time. Data Analysis A total of 157 patients provided complete data for these analyses. Descriptive statistics and frequency distributions were generated for the patients demographic and diseaserelated characteristics. Pearson s product moment coefficients were calculated to evaluate the relationships between the selected variables. A blockwise, hierarchical multiple regression analysis was done to further explore the relationships between the selected variables, using QOL as the dependent variable. 28 Variables were entered into the model in the following order: Block I: pain characteristics (pain intensity, pain duration, pain relief, and meaning of pain); Block II: physical and social functioning; and Block III: depression. Depression was entered into the model last as it was assumed to be affected by decreased physical functioning. A P-value of! 0.05 was considered statistically significant. Results Sample Demographics The demographic and disease characteristics of the patients are summarized in Table 2. The mean age of the patients was 60.2 years (SD ), range years. The majority of the sample was female, married, cohabiting, and Caucasian. The majority of the sample was Table 2 Demographic and Disease Characteristics of the Sample (n [ 157) Sample Characteristics n (%) Sex Female 108 (68.8) Male 49 (31.2) Lives alone Yes 43 (27.6) No 113 (72.4) Marital status Married/partnered 86 (54.8) Never married 11 (7.0) Divorced 29 (18.5) Other 31 (19.7) Ethnicity Caucasian 136 (86.6) Other 21 (13.4) Employment Full time/part time 24 (15.3) Disability 44 (28.0) Retired 66 (42.0) Other 23 (14.7) Diagnosis Breast 75 (47.8) Prostate 17 (10.8) Lung 20 (12.7) Other 45 (28.7) Current therapy a Chemotherapy 69 (43.9) Hormonal therapy 47 (29.9) Radiation therapy 30 (19.1) Biotherapy 4 (2.5) No treatment 19 (12.1) a Some patients were receiving more than one treatment. diagnosed with breast cancer and was currently receiving cancer treatment. Characteristics of the Pain Problem and Pain Relief The characteristics of the pain problem and pain relief scores are listed in Table 3. The mean score for pain now was 3.8 (SD 5 2.1) and the mean score for worst pain was 7.0 (SD 5 2.0). According to Serlin et al. s severity of pain categories, % (n 5 14) reported mild pain, 24.8% (n 5 39) reported moderate pain, and 66.2% (n 5 104) reported severe pain. As shown in Table 3, 88% of the sample had been in pain for more than 2 months, and almost 38% reported a pain duration of more than 1 year. The mean score for how upsetting the pain was reached 6.5 (SD 3.0, range 0--10). Of note, 69.4% of the sample reported a score of 5 or higher on this measure. Finally, the mean score on the pain relief scale was 67.1% (SD , range %).

6 Vol. 30 No. 3 September 2005 Predictors of QOL 239 Table 3 Pain Characteristics (n [ 157) Pain Characteristic Mean (SD) Range Pain intensity Pain now 3.8 (2.1) 0--9 Average pain 4.3 (1.7) 1--8 Least pain 1.9 (1.5) 0--7 Worst pain 7.0 (2.0) Pain relief Percent of pain relief in 67.1 (20.6) the past week Meaning of pain How upsetting is your pain? 6.5 (3.0) (0 5 none to 10 5 a great deal) n % Pain duration Less than 1 week to 2 weeks About 1 month to 6 months months to 1 year More than 1 year QOL, Social Functioning, Physical Functioning, and Depression The single item QOL score mean was 6.7 (SD 5 2.4, range 0--10). The correlation between the single item global QOL score and the total scale score (the entire QOL instrument with the global item removed) was The mean score for the social functioning subscale of the SF-36 was 51.4 (SD ) with a range of Approximately 60% of the sample had a score # 50. The mean KPS score was 69.6 (SD ). The mean score on the depression subscale of the POMS was 4.6 (SD 5 4.1), with a range of 0 to 20. Approximately 19% of the sample did not report any depression and 10.2% reported a depression score $ 10. The Interrelationships Among the Study Variables As outlined in Table 4, all of the variables, were significantly correlated with QOL. The pain characteristics (i.e., pain intensity, meaning of pain, pain duration, and pain relief) were significantly, but weakly, correlated with QOL, and social functioning, depression, and physical functioning were moderately to strongly correlated with QOL. Based on Serlin et al. s severity of pain categories, 29 patients in the severe pain category reported a significantly poorer QOL than patients with mild or moderate pain [F(2,154) 5 3.9, P ]. Patients who reported mild pain had a mean QOL score of 8.2 (SD 5 2.0), those with moderate pain had a QOL score of 6.9 (SD 5 2.1), and those in severe pain had a QOL score of 6.3 (SD 5 2.5). The Impact of the Different Variables on QOL The result of the regression analysis is shown in Table 5. In the first step of the regression analysis, pain characteristics (i.e., pain intensity, pain duration, pain relief, and meaning of pain) were entered into the model. These variables had a small impact on QOL, explaining 8.6% of the variance in QOL [F(4,152) 5 3.6, P ]. Pain relief was the only pain characteristic that demonstrated a controlled statistical association with QOL. When physical functioning and social functioning were entered into the model in Block II, both of these variables demonstrated significant relationships with QOL and the percent of explained variance increased by 19.8% [F(2,150) , P! ] to 28.4% [F(6,150) 5 9.9, Table 4 Intercorrelations (Pearsons r) Between the Selected Variables in the Model QOL Physical Functioning Social Functioning Depression Pain Intensity Meaning of Pain Pain Duration Pain Relief Physical functioning 0.46 a d Social functioning 0.43 a 0.51 a d Depression a b a d Pain intensity c d c 0.10 d Meaning of pain d c a 0.24 b 0.46 a d Pain duration d d 0.20 c d Pain relief 0.19 c 0.21 c 0.19 c c d a Correlation is significant at the P # level. b Correlation is significant at the P! level. c Correlation is significant at the P! 0.01 level. d Correlation is significant at the P! 0.05 level.

7 240 Rustøen et al. Vol. 30 No. 3 September 2005 P! ]. However, none of the pain characteristics made a significant contribution to QOL. When depression was entered into the model in the final step (Block III), only physical functioning and depression contributed significantly to QOL. The percent of explained variance for the entire model increased by 14% [F(1,149) , P! ] to 42.4% [F(7,149) , P! ]. Discussion This study is the first to test the relationships among several pain and patient characteristics and their impact on QOL in a sample of oncology outpatients with pain from bone metastasis. The three most important variables that predicted the greatest amount of variance in QOL in this sample of patients in chronic pain were depression, physical functioning, and social functioning. This finding supports earlier research that identified physical well-being, psychological well-being, and social well-being as important domains of QOL. 10 However, the regression analysis demonstrated that depression had the greatest impact on QOL in this sample of oncology outpatients with pain. While several studies have demonstrated an association between cancer pain and depression, 2,16,30,31 this study suggests that depression may be one of the most important factors influencing QOL and may warrant an intervention independent of pain management in this patient population. It should be noted Table 5 Results of a Blockwise Hierarchical Regression Analysis of the Effects of Selected Variables on Quality of Life (n [ 157) Variables in the model r a Standardized Regression Coefficients Block I Block II Block III Pain intensity Pain duration Pain relief Meaning of pain Physical functioning Social functioning Depression Cumulative percent of explained variance b Coefficients in bold are significant (P! 0.05). a r 5 correlation between the variable and QOL. b R square. that only 5.7% of patients in this study were on an antidepressant medication. Our data clearly demonstrate that physical functioning is a critical component of QOL in oncology outpatients with pain. In addition, physical functioning was significantly correlated with all of the other variables that were tested in this model except for pain duration. The strongest positive correlation was found between physical functioning and social functioning. Of note, for the pain characteristics, the strongest correlation was found between physical functioning and pain relief such that the better the pain relief the higher the patients level of physical functioning. Based on the results of the regression analysis, it is not clear what role social functioning plays in the QOL of oncology patients with pain. While studies have shown that cancer pain interferes with social functioning 5,32 and with work activities, 12 and this study found modest negative correlations between pain intensity (r ) and meaning of pain (r ) and QOL, when depression was entered into the regression analysis, social functioning no longer showed a direct effect on QOL. This finding may indicate that depression functions as an intervening variable in the relationship between social functioning and QOL. A surprising finding from this study, in contrast to many of the hypotheses put forth by Portenoy, 9 is that only one of the pain characteristics tested in the model, namely pain relief, made significant unique contributions to the percent of explained variance in QOL. One potential explanation for this finding is that because these patients had been in a significant amount of persistent pain for a prolonged period of time, they may have experienced a response shift in their QOL. 33 In addition, the association between pain intensity and pain interference appears to be non-linear, 34 as pain intensity beyond a certain level (defined as moderate intensity) does not impact appreciably on pain interference. Thus, patients with mild and moderate pain reported a better QOL than patients with severe cancer pain. Because over 91% of our sample had moderate to severe pain, the variance in pain intensity may have been too small to demonstrate a significant relationship with QOL. These two hypotheses warrant

8 Vol. 30 No. 3 September 2005 Predictors of QOL 241 testing in a larger sample of oncology outpatients with more variance in their pain intensity scores. It is interesting to note that the only pain characteristic that demonstrated significant correlations with all of the other variables that were tested in the model was meaning of pain. The importance of the meaning of symptoms, such as pain, to cancer patients has been emphasized in recent years. 35 In fact, work by Rhodes and McDaniel 36 demonstrates that the meaning that people assign to physical sensations may have profound effects on their QOL. The findings from the present study do not fully support all of the hypotheses suggested by Portenoy about the relationships between pain and QOL. The fact that both pain intensity and psychological distress had a negative effect on QOL, but accounted for a very modest proportion of the variance in QOL is an important finding that warrants further investigation. The findings from this study suggest that both depression and physical function partly function as intervening variables between pain characteristics and QOL, and impact directly on the QOL of oncology outpatients with cancer pain. An additional hypothesis that warrants further investigation based on the findings from this study is the meaning of the pain to the patient. Portenoy s hypothesis that the intensity of the pain, the psychological distress resulting from the pain, and QOL are strongly influenced by pain relief was not supported in this study. On the other hand, pain intensity, psychological distress, and QOL were influenced by social functioning, which supports another of Portenoy s hypotheses. In summary, the key factors that made significant contributions to the explained variance in QOL were psychological distress, physical functioning, and social functioning, in part because they functioned as intervening variables between pain characteristics and QOL. Because some studies found sex differences 37 and age differences 6 in pain and QOL, prior to performing the regression analysis, we tested for sex differences in QOL as well as the relationship between age and QOL. A nonsignificant relationship was found between age and QOL (r ) and no differences were found in the QOL scores of the men (mean 5 6.5) and women (mean 5 6.7) in this study. Therefore, neither of these variables were entered into the regression analysis. One limitation of this study that must be noted is that, since this was a secondary analysis, the variables that were used to test the relationships described in Portenoy s model were not chosen a priori for model testing. Rather, the variables selected for testing in some cases were approximations for the concepts (e.g., meaning of pain was measured as how distressing the pain was to the patients) that were available in the data set. In addition, these findings may not be generalizable to the entire population of oncology outpatients with pain from bone metastasis because the sample was primarily Caucasian women with breast cancer. Despite these limitations, the findings from this study extend our understanding of the relationships between various patient and pain characteristics and QOL. Longitudinal studies are needed to determine how pain and QOL change over time and whether a response shift does indeed occur. In addition, findings from the regression analysis suggest that endpoints of cancer pain studies should include at a minimum not only measures of various pain characteristics but also measures of depression, physical functioning, and QOL. References 1. Ferrans CE. Development of a quality of life index for patients with cancer. Oncol Nurs Forum 1990;17: Ferrell B, Grant M, Padilla G, et al. The experience of pain and perceptions of quality of life: validation of a conceptual model. Hosp J 1991; 7: Miaskowski C, Dibble SL. The problem of pain in outpatients with breast cancer. Oncol Nurs Forum 1995;22: Rummans TA, Frost M, Suman VJ, et al. Quality of life and pain in patients with recurrent breast and gynecologic cancer. Psychosomatics 1998;39: Strang P, Qvarner H. Cancer-related pain and its influence on quality of life. Anticancer Res 1990; 10: Sandblom G, Carlsson P, Sigsjo P, Varenhorst E. Pain and health-related quality of life in a geographically defined population of men with prostate cancer. Br J Cancer 2001;85: Burrows M, Dibble SL, Miaskowski C. Differences in outcomes among patients experiencing

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