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Research Report
Predictive factors of overall quality of life in advanced cancer patients using EORTC QLQ-C30 Expert Rev. Pharmacoecon. Outcomes Res. 14(1), 139–146 (2014)
Gemma Cramarossa, Liang Zeng, Liying Zhang, Ling-Ming Tseng, Ming-Feng Hou, Alysa Fairchild, Vassilios Vassiliou, Reynaldo Jesus-Garcia, Mohamed A Alm El-Din, Aswin Kumar, Fabien Forges, Wei-Chu Chie, Arjun Sahgal, Henry Lam, Natalie Pulenzas and Edward Chow* *Author for correspondence: Tel.: +1 416 480 4998 Fax: +1 416 480 6002 [email protected] For a full list of author affiliations, please see page 146.
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Objective: To identify which domains/symptoms from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) were predictive of overall quality of life (QoL) in advanced cancer patients. Methods: Four hundred and forty seven patients with brain metastases or bone metastases from seven countries were enrolled with regression analysis to determine the predictive value of the QLQ-C30 functional/ symptom scores for patient reported overall QoL (question 30), overall health (question 29) and the global health status domain (questions 29 and 30). Results: Worse role functioning, social functioning, fatigue and financial problems were the most significant predictive factors for worse QoL. In the bone metastases subgroup (n = 400), role functioning, fatigue and financial problems were the most significant predictors. In patients with brain metastases (n = 47), none of the EORTC domains significantly predicted worse QOL. Conclusion: Deterioration of certain QLQ-C30 functional/symptom scores significantly contributes to worse QoL, overall health and global health status. KEYWORDS: advanced cancer • EORTC QLQ-C30 • metastatic cancer • quality of life • symptom control
Health care providers refer to improvement of quality of life (QoL) as the main treatment goal for advanced cancer patients due to their poor prognosis [1]. Advanced cancer patients include those with bone metastases (BM) and brain metastases (BN), which impose additional functional deficits and thus increase patients’ symptom burden. Patients with BM commonly suffer skeletal complications, including bone pain, pathologic fractures and spinal cord compression which lead to a decline their QoL [2]. BN are a common neurological complication which cancer patients may experience [3]. Median survival of BN patients is approximately 4 months following whole brain radiation therapy, thus maintenance of QoL is the main focus for these patients due to their poor prognosis [3–6]. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) is an internationally validated QoL assessment tool for cancer patients [7]. The EORTC QLQ-C30 is composed of 15 domains: five 10.1586/14737167.2014.864560
functional scales (physical, role, cognitive, emotional and social), three symptom scales (fatigue, pain and nausea/vomiting), six single item measures (dyspnea, insomnia, loss of appetite, constipation, diarrhea and financial troubles) and a global health/QoL scale [7]. Patient reported scores are used to assist health care professionals in management of QoL. The 28 symptom/functional items are ranked on a scale of 1–4, from 1‘not at all’ to 4 ‘very much’. The last two items on the questionnaire ask patients to rate their overall health and QoL in the past week, and are scored on a scale of 1–7, with ‘1’ being very poor and ‘7’ being excellent. The EORTC domains have previously demonstrated construct validity [8]. Presence of the QoL issues assessed by the QLQ-C30 contributes to worsening patients’ overall QoL. Multiple symptom/functional concerns may be associated with poorer patient outcome [6,9–11]. By identifying those issues most related to QoL, overall health and global health status, health-care professionals can
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ISSN 1473-7167
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Cramarossa, Zeng, Zhang et al.
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triage management strategies most beneficial to the patient. The objective of this study is to identify which domains/ symptoms from the EORTC QLQ-C30 were significant predictors of overall QoL in patients with metastatic cancer. Materials & methods Participants
The EORTC QLQ-C15-PAL was completed at baseline by all willing and able advanced cancer patients from seven countries: Brazil, Canada, Cyprus, Egypt, France, India and Taiwan, between July 2008 and March 2011. The questionnaire was completed at baseline prior to radiotherapy consultation and at 1-month following treatment for those who went on to receive radiotherapy; those subjects who did not receive treatment or passed away, account for the drop-out at follow-up. Ethics approval was granted by the institutional research ethics board. Statistics
Data was collected and summarized for the total patient sample as well as for both the BM and BN subgroups. Country of accrual, primary cancer, gender, education level, employment status, cohabitants and married status were summarized with proportions, and age and Karnofsky performance status (KPS) were described using mean, standard deviation (SD), median and range. Natural log-transformation was applied to the QLQ-C30 individual items and domain scores to normalize the distribution; p < 0.05 was considered as statistical significance. Simple univariate linear regression analysis was conducted, followed by backward selection procedure in the multivariate linear regression analysis, to identify the most significant associations between question 30 ‘overall QoL’, question 29 ‘overall health’ and questions 29 and 30 combined ‘global health status’ and the other 14 domain scores. The variables with p < 0.10 from univariate analysis were input to the multivariate backward selection procedure analysis. A Bonferroni-adjusted p < 0.002 (0.05/30 items) was considered statistically significant for multivariate analysis to adjust for multiple comparisons. Standard error (SE), mean square error (MSE) and coefficient of the regression analyses were calculated for each predictor. MSE is used to estimate error variance and is calculated by dividing the residual sum of squares by the degrees of freedom. A lower MSE indicates a better fit for the model. For functional domains, the higher the score on the questionnaire the better the function is. In contrast, for symptom domains, a higher score indicates worse symptom burden. All analyses were conducted by Statistical Analysis Software (SAS version 9.2 for Windows).
(10.7%) and prostate (10.3%). There were more female participants in the study (73.8 vs 26.2%). Four hundred patients had bone metastases and only 47 had brain metastases. Seventy percent of the total patient sample had received previous systemic treatment before the baseline measure. Three bone metastases patients dropped out of the study after the collection of demographic information, thus EORTC QLQ-C30 questionnaire data is available for 444 patients at baseline. All domain scores (physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning, fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation and financial problems) except for diarrhea were significantly associated with the final QoL item. Multivariate analysis was applied to determine the most significant predictors of the 13 significant domains. Role functioning (p < 0.0001), social functioning (p < 0.0001), fatigue (p < 0.0001) and financial problems (p = 0.0011) were most predictive of overall QoL in all patients (TABLE 2). Fatigue had the largest absolute value coefficient (-0.093), followed by role functioning (0.061), social functioning (0.056) and financial problems (-0.034), indicating that a single point increase in fatigue would incur the greatest change in patient reported QoL, compared with the other domains. At the 1 month follow-up in 380 patients, univariate analysis revealed all domain scores except diarrhea were significantly correlated to patient reported QoL. Social functioning (coefficient of 0.123), pain (-0.053) and appetite loss (-0.038) remained statistically significant after multivariate analysis. Bone metastases subgroup: overall QoL
The QLQ-C30 was completed by 400 BM patients. The median age of the subgroup was 57 years (range: 26–95) with a median KPS of 80 (range: 30–100). The predominant primary cancers were breast (68.3%) and prostate (11.5%). All domain scores, except diarrhea, were significantly related to QoL (as assessed by item 30). Multivariate analysis identified role functioning (p < 0.0001), fatigue (p < 0.0001) and financial problems (p < 0.0001) as the most significant predictors of patient reported QoL. Fatigue had the largest absolute value coefficient (-0.105), followed by role functioning (0.089) and financial problems (-0.047), indicating that of the three domains, a single point increase in fatigue would incur the greatest change in patient reported QoL. Univariate linear regression analysis at follow-up in 349 patients revealed all domains except diarrhea were statistically significant. Multivariate linear regression analysis revealed that social functioning (coefficient 0.129), pain (-0.058) and appetite loss (-0.037) remained statistically significant.
Results
Brain metastases subgroup: overall QoL
Total patient sample: overall QoL
Forty seven patients with BN completed with QLQ-C30. The median age of the subgroup was 61 years (range: 24–86) with a median KPS of 70 (range: 40–100). The predominant primary cancers were lung (36.2%) and breast (34%). At baseline, no domains were significantly associated with
Demographic information is available for 447 patients (TABLE 1). The median patient age was 57 years (range: 24–95) and patients had a median KPS of 80 (range: 30–100). The most common primary cancers were of the breast (64.7%), lung 140
Expert Rev. Pharmacoecon. Outcomes Res. 14(1), (2014)
Predictive values for QoL in patients with bone metastases
Research Report
Table 1. Patient characteristics. Socio-demographic data
BM: n = 400 (n; %)
BN: n = 47 (n; %)
Total: n = 447 (n; %)
Taiwan
225 (56.25)
0 (0.00)
225 (50.34)
Canada
120 (30.00)
27 (57.45)
147 (32.89)
Cyprus
19 (4.75)
14 (29.79)
33 (7.38)
Brazil
11 (2.75)
6 (12.77)
12 (2.68)
Egypt
12 (3.00)
0 (0.00)
17 (3.80)
India
7 (1.75)
0 (0.00)
7 (1.57)
France
6 (1.50)
0 (0.00)
6 (1.34)
Mean (SD)
58.0 (13.1)
60.6 (11.9)
58.3 (13.0)
Median (range)
57 (26–95)
61 (24–86)
57 (24–95)
Mean (SD)
83.0 (16.8)
70.4 (13.3)
81.7 (16.8)
Median (range)
80 (30 100)
70 (40 100)
80 (30 100)
Female
303 (75.75)
27 (57.45)
330 (73.83)
Male
97 (24.25)
20 (42.55)
117 (26.17)
Elementary school
25 (14.20)
4(8.89)
29 (13.12)
High school
67 (38.07)
21 (46.67)
88 (39.82)
University
46 (26.14)
15 (33.33)
61 (27.60)
Masters or PhD
12 (6.82)
3 (6.67)
16 (6.79)
Others
26 (14.77)
2 (4.44)
28 (12.67)
Retired
91 (51.12)
22 (46.81)
113 (50.22)
Employed
48 (26.97)
12 (25.53)
60 (26.67)
Unemployed
38 (21.35)
13 (27.66)
51 (22.67)
Others
1 (0.56)
0 (0.00)
1 (0.44)
Spouse
81 (45.51)
23 (48.94)
104 (46.22)
Spouse and children
39 (21.91)
14 (29.79)
53 (23.56)
Alone
27 (15.17)
6 (12.77)
33 (14.67)
Children
18 (10.11)
2 (4.26)
20 (8.89)
Others
13 (7.30)
2 (4.26)
15 (6.67)
Married
116 (65.17)
35 (74.47)
151 (67.11)
Widowed
21 (11.80)
6 (12.77)
27 (12.00)
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Country
Age at baseline (years)
KPS at baseline
Gender
Education level
Employment status
Cohabitants
Married status
BM: Bone metastases; BN: Brain metastases; KPS: Karnofsky performance status; SD: Standard deviation.
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Cramarossa, Zeng, Zhang et al.
Table 1. Patient characteristics (cont.). Socio-demographic data
BM: n = 400 (n; %)
BN: n = 47 (n; %)
Total: n = 447 (n; %)
Single
15(8.43)
5(10.64)
20(8.89)
Other
26 (14.60)
1 (2.13)
27 (12.00)
Breast
273 (68.25)
16 (34.04)
289 (64.65)
Lung
31 (7.75)
17 (36.17)
48 (10.74)
Prostate
46 (11.50)
0 (0.00)
46 (10.29)
Gastrointestinal
10 (2.50)
6 (12.77)
16 (3.58)
Renal cell
9 (2.25)
2 (4.26)
11 (2.46)
Others
31 (7.75)
6 (12.77)
37 (8.28)
Outpatient
367 (91.98)
40 (85.11)
407 (91.26)
Inpatient
32 (8.02)
7 (14.89)
39 (8.74)
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Married status (cont.)
Baseline clinical data Primary cancer site
Patients status
BM: Bone metastases; BN: Brain metastases; KPS: Karnofsky performance status; SD: Standard deviation.
patient reported QoL (as assessed by item 30). Multivariate linear regression analysis also revealed no significant relationship with question 30. At follow-up in 30 patients, both univariate and multivariate analysis did not result in any significant predictors. Total patient sample:– overall health
All domain scores except for diarrhea were significantly associated with the overall health item. Multivariate analysis revealed role functioning (p < 0.0001), fatigue (p < 0.0001) and nausea/vomiting (p = 0.0002) as most predictive of overall health (TABLE 3). Fatigue had the largest absolute value coefficient (-0.093), followed by role functioning (0.078) and nausea/vomiting (-0.043). At the 1 month follow-up, univariate analysis revealed all domain scores except constipation and diarrhea were significantly correlated to patient reported overall health. Social functioning (coefficient of 0.077), fatigue (-0.062) and pain (-0.051) remained statistically significant after multivariate analysis. Bone metastases subgroup: overall health
All domain scores except diarrhea were significantly related to overall health. Multivariate analysis identified role functioning (p < 0.0001), fatigue (p < 0.0001) and nausea/vomiting (p < 0.0001) were the most significant predictors of patient reported overall health in this subgroup. Fatigue had the largest absolute value coefficient (-0.090), followed by role functioning (0.087), and nausea/vomiting (-0.050). Univariate analysis at follow-up revealed all domains except insomnia, constipation and diarrhea were statistically significant. Multivariate linear regression analysis revealed that social functioning (coefficient 142
0.081), fatigue (-0.060) and pain (-0.055) remained statistically significant. Brain metastases subgroup: overall health
At baseline, only fatigue significantly associated with patient reported overall health (as assessed by item 29). Multivariate analysis also revealed fatigue as a significant predictor (p = 0.0011; coefficient -0.100). At follow-up, both univariate and multivariate linear regression analysis did not result in any significant predictors in the BN subgroup. Total patient sample: global health status
All domain scores except for diarrhea were significantly associated with the global health status items. Multivariate analysis revealed role functioning (p < 0.0001), fatigue (p = 0.0002) and financial problems (p = 0.0005) as most predictive of global health status (TABLE 4). Role functioning had the largest absolute value coefficient (0.171), followed by fatigue (-0.143), and financial problems (-0.071). At the 1 month follow-up, univariate analysis revealed all domain scores except insomnia, constipation and diarrhea were significantly correlated to global health status. Social functioning (coefficient of 0.197), pain (-0.087) and dyspnea (-0.052) remained statistically significant after multivariate analysis. Bone metastases subgroup: global health status
All domain scores except diarrhea were significantly related to global health status (as assessed by items 29 and 30). Multivariate analysis identified role functioning (p < 0.0001), nausea/ vomiting (p = 0.0001) and financial problems (p = 0.0001) were the most significant predictors of global health status. Expert Rev. Pharmacoecon. Outcomes Res. 14(1), (2014)
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Predictive values for QoL in patients with bone metastases
Role functioning had the largest absolute value coefficient (0.216), followed by and nausea/vomiting (-0.095) and financial problems (-0.085). Univariate analysis at follow-up revealed all domains except insomnia, constipation and diarrhea were statistically significant. Multivariate analysis revealed that social functioning (coefficient 0.212) and pain (-0.104) remained statistically significant. Brain metastases subgroup: global health status
At baseline, no domains were significantly associated with global health status (as assessed by item 29 and 30). Multivariate analysis also revealed no significant relationship with global health status. At follow-up, both univariate and multivariate linear regression analysis did not result in any significant predictors. Discussion
Patient reported QoL as part of the EORTC QLQ-C30 is influenced by a number of other symptoms assessed by the same tool. Palliative patient care may benefit from paying special attention to management of the most significant predictors of QoL, including those identified in the present study and in the literature. The present study analyzed predictive factors in the total patient sample as well in BM and BN subgroups with varying primary cancers. The deterioration of domain/symptom scores may vary in different patient subgroups, evidenced by the dissimilarity in BM and BN subgroup results. This is the first known study to simultaneously analyze predictors of QoL, overall health and global health status to determine if predictive factors are constant regardless of the item used for correlation analysis. Results indicate that there are similar predictors among the three. For the total patient sample at baseline, role functioning and fatigue were significant predictors of QoL, overall health and global health status. At follow-up, social functioning was also a significant predictor for all three items. For the BM subgroup, role functioning was a significant predictor for all three items at baseline, and at follow-up social functioning significantly correlated with QoL, overall health and global health status. These similarities indicate that regardless of the item utilized for correlation analysis, many of the same domains affect cancer patients’ overall condition. There are a few published studies which have conducted similar analyses to determine which domains significantly correlate with the QoL question of the EORTC QLQ-C30. Beijer et al. published a study on pre-terminal cancer patients which found that of the QLQ-C30 domains, fatigue, role functioning, physical functioning, social functioning, nausea, cognitive functioning, appetite loss, dyspnea and emotional functioning had the strongest correlation to QoL with univariate analysis [12]. Multivariate analysis revealed fatigue and social functioning were the major contributors to QoL. In the current study, fatigue was highly significant with overall QoL, health and global health status in the total patient sample at baseline, and social functioning was significant with QoL at baseline and follow-up in the total patient sample. Social functioning www.expert-reviews.com
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Table 2. Multivariate linear regression analysis of most predictive factors of patient reported QoL (question 30) in the total patient sample at baseline. Domain†
Coefficient
SE
p-value
Intercept = 1.282 (SE 0.117), MSE = 0.157 Role functioning
0.061
0.015
Research Report
Predictive factors of overall quality of life in advanced cancer patients using EORTC QLQ-C30 Expert Rev. Pharmacoecon. Outcomes Res. 14(1), 139–146 (2014)
Gemma Cramarossa, Liang Zeng, Liying Zhang, Ling-Ming Tseng, Ming-Feng Hou, Alysa Fairchild, Vassilios Vassiliou, Reynaldo Jesus-Garcia, Mohamed A Alm El-Din, Aswin Kumar, Fabien Forges, Wei-Chu Chie, Arjun Sahgal, Henry Lam, Natalie Pulenzas and Edward Chow* *Author for correspondence: Tel.: +1 416 480 4998 Fax: +1 416 480 6002 [email protected] For a full list of author affiliations, please see page 146.
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Objective: To identify which domains/symptoms from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) were predictive of overall quality of life (QoL) in advanced cancer patients. Methods: Four hundred and forty seven patients with brain metastases or bone metastases from seven countries were enrolled with regression analysis to determine the predictive value of the QLQ-C30 functional/ symptom scores for patient reported overall QoL (question 30), overall health (question 29) and the global health status domain (questions 29 and 30). Results: Worse role functioning, social functioning, fatigue and financial problems were the most significant predictive factors for worse QoL. In the bone metastases subgroup (n = 400), role functioning, fatigue and financial problems were the most significant predictors. In patients with brain metastases (n = 47), none of the EORTC domains significantly predicted worse QOL. Conclusion: Deterioration of certain QLQ-C30 functional/symptom scores significantly contributes to worse QoL, overall health and global health status. KEYWORDS: advanced cancer • EORTC QLQ-C30 • metastatic cancer • quality of life • symptom control
Health care providers refer to improvement of quality of life (QoL) as the main treatment goal for advanced cancer patients due to their poor prognosis [1]. Advanced cancer patients include those with bone metastases (BM) and brain metastases (BN), which impose additional functional deficits and thus increase patients’ symptom burden. Patients with BM commonly suffer skeletal complications, including bone pain, pathologic fractures and spinal cord compression which lead to a decline their QoL [2]. BN are a common neurological complication which cancer patients may experience [3]. Median survival of BN patients is approximately 4 months following whole brain radiation therapy, thus maintenance of QoL is the main focus for these patients due to their poor prognosis [3–6]. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) is an internationally validated QoL assessment tool for cancer patients [7]. The EORTC QLQ-C30 is composed of 15 domains: five 10.1586/14737167.2014.864560
functional scales (physical, role, cognitive, emotional and social), three symptom scales (fatigue, pain and nausea/vomiting), six single item measures (dyspnea, insomnia, loss of appetite, constipation, diarrhea and financial troubles) and a global health/QoL scale [7]. Patient reported scores are used to assist health care professionals in management of QoL. The 28 symptom/functional items are ranked on a scale of 1–4, from 1‘not at all’ to 4 ‘very much’. The last two items on the questionnaire ask patients to rate their overall health and QoL in the past week, and are scored on a scale of 1–7, with ‘1’ being very poor and ‘7’ being excellent. The EORTC domains have previously demonstrated construct validity [8]. Presence of the QoL issues assessed by the QLQ-C30 contributes to worsening patients’ overall QoL. Multiple symptom/functional concerns may be associated with poorer patient outcome [6,9–11]. By identifying those issues most related to QoL, overall health and global health status, health-care professionals can
Ó 2014 Informa UK Ltd
ISSN 1473-7167
139
Research Report
Cramarossa, Zeng, Zhang et al.
Expert Review of Pharmacoeconomics & Outcomes Research Downloaded from informahealthcare.com by Nanyang Technological University on 04/28/15 For personal use only.
triage management strategies most beneficial to the patient. The objective of this study is to identify which domains/ symptoms from the EORTC QLQ-C30 were significant predictors of overall QoL in patients with metastatic cancer. Materials & methods Participants
The EORTC QLQ-C15-PAL was completed at baseline by all willing and able advanced cancer patients from seven countries: Brazil, Canada, Cyprus, Egypt, France, India and Taiwan, between July 2008 and March 2011. The questionnaire was completed at baseline prior to radiotherapy consultation and at 1-month following treatment for those who went on to receive radiotherapy; those subjects who did not receive treatment or passed away, account for the drop-out at follow-up. Ethics approval was granted by the institutional research ethics board. Statistics
Data was collected and summarized for the total patient sample as well as for both the BM and BN subgroups. Country of accrual, primary cancer, gender, education level, employment status, cohabitants and married status were summarized with proportions, and age and Karnofsky performance status (KPS) were described using mean, standard deviation (SD), median and range. Natural log-transformation was applied to the QLQ-C30 individual items and domain scores to normalize the distribution; p < 0.05 was considered as statistical significance. Simple univariate linear regression analysis was conducted, followed by backward selection procedure in the multivariate linear regression analysis, to identify the most significant associations between question 30 ‘overall QoL’, question 29 ‘overall health’ and questions 29 and 30 combined ‘global health status’ and the other 14 domain scores. The variables with p < 0.10 from univariate analysis were input to the multivariate backward selection procedure analysis. A Bonferroni-adjusted p < 0.002 (0.05/30 items) was considered statistically significant for multivariate analysis to adjust for multiple comparisons. Standard error (SE), mean square error (MSE) and coefficient of the regression analyses were calculated for each predictor. MSE is used to estimate error variance and is calculated by dividing the residual sum of squares by the degrees of freedom. A lower MSE indicates a better fit for the model. For functional domains, the higher the score on the questionnaire the better the function is. In contrast, for symptom domains, a higher score indicates worse symptom burden. All analyses were conducted by Statistical Analysis Software (SAS version 9.2 for Windows).
(10.7%) and prostate (10.3%). There were more female participants in the study (73.8 vs 26.2%). Four hundred patients had bone metastases and only 47 had brain metastases. Seventy percent of the total patient sample had received previous systemic treatment before the baseline measure. Three bone metastases patients dropped out of the study after the collection of demographic information, thus EORTC QLQ-C30 questionnaire data is available for 444 patients at baseline. All domain scores (physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning, fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation and financial problems) except for diarrhea were significantly associated with the final QoL item. Multivariate analysis was applied to determine the most significant predictors of the 13 significant domains. Role functioning (p < 0.0001), social functioning (p < 0.0001), fatigue (p < 0.0001) and financial problems (p = 0.0011) were most predictive of overall QoL in all patients (TABLE 2). Fatigue had the largest absolute value coefficient (-0.093), followed by role functioning (0.061), social functioning (0.056) and financial problems (-0.034), indicating that a single point increase in fatigue would incur the greatest change in patient reported QoL, compared with the other domains. At the 1 month follow-up in 380 patients, univariate analysis revealed all domain scores except diarrhea were significantly correlated to patient reported QoL. Social functioning (coefficient of 0.123), pain (-0.053) and appetite loss (-0.038) remained statistically significant after multivariate analysis. Bone metastases subgroup: overall QoL
The QLQ-C30 was completed by 400 BM patients. The median age of the subgroup was 57 years (range: 26–95) with a median KPS of 80 (range: 30–100). The predominant primary cancers were breast (68.3%) and prostate (11.5%). All domain scores, except diarrhea, were significantly related to QoL (as assessed by item 30). Multivariate analysis identified role functioning (p < 0.0001), fatigue (p < 0.0001) and financial problems (p < 0.0001) as the most significant predictors of patient reported QoL. Fatigue had the largest absolute value coefficient (-0.105), followed by role functioning (0.089) and financial problems (-0.047), indicating that of the three domains, a single point increase in fatigue would incur the greatest change in patient reported QoL. Univariate linear regression analysis at follow-up in 349 patients revealed all domains except diarrhea were statistically significant. Multivariate linear regression analysis revealed that social functioning (coefficient 0.129), pain (-0.058) and appetite loss (-0.037) remained statistically significant.
Results
Brain metastases subgroup: overall QoL
Total patient sample: overall QoL
Forty seven patients with BN completed with QLQ-C30. The median age of the subgroup was 61 years (range: 24–86) with a median KPS of 70 (range: 40–100). The predominant primary cancers were lung (36.2%) and breast (34%). At baseline, no domains were significantly associated with
Demographic information is available for 447 patients (TABLE 1). The median patient age was 57 years (range: 24–95) and patients had a median KPS of 80 (range: 30–100). The most common primary cancers were of the breast (64.7%), lung 140
Expert Rev. Pharmacoecon. Outcomes Res. 14(1), (2014)
Predictive values for QoL in patients with bone metastases
Research Report
Table 1. Patient characteristics. Socio-demographic data
BM: n = 400 (n; %)
BN: n = 47 (n; %)
Total: n = 447 (n; %)
Taiwan
225 (56.25)
0 (0.00)
225 (50.34)
Canada
120 (30.00)
27 (57.45)
147 (32.89)
Cyprus
19 (4.75)
14 (29.79)
33 (7.38)
Brazil
11 (2.75)
6 (12.77)
12 (2.68)
Egypt
12 (3.00)
0 (0.00)
17 (3.80)
India
7 (1.75)
0 (0.00)
7 (1.57)
France
6 (1.50)
0 (0.00)
6 (1.34)
Mean (SD)
58.0 (13.1)
60.6 (11.9)
58.3 (13.0)
Median (range)
57 (26–95)
61 (24–86)
57 (24–95)
Mean (SD)
83.0 (16.8)
70.4 (13.3)
81.7 (16.8)
Median (range)
80 (30 100)
70 (40 100)
80 (30 100)
Female
303 (75.75)
27 (57.45)
330 (73.83)
Male
97 (24.25)
20 (42.55)
117 (26.17)
Elementary school
25 (14.20)
4(8.89)
29 (13.12)
High school
67 (38.07)
21 (46.67)
88 (39.82)
University
46 (26.14)
15 (33.33)
61 (27.60)
Masters or PhD
12 (6.82)
3 (6.67)
16 (6.79)
Others
26 (14.77)
2 (4.44)
28 (12.67)
Retired
91 (51.12)
22 (46.81)
113 (50.22)
Employed
48 (26.97)
12 (25.53)
60 (26.67)
Unemployed
38 (21.35)
13 (27.66)
51 (22.67)
Others
1 (0.56)
0 (0.00)
1 (0.44)
Spouse
81 (45.51)
23 (48.94)
104 (46.22)
Spouse and children
39 (21.91)
14 (29.79)
53 (23.56)
Alone
27 (15.17)
6 (12.77)
33 (14.67)
Children
18 (10.11)
2 (4.26)
20 (8.89)
Others
13 (7.30)
2 (4.26)
15 (6.67)
Married
116 (65.17)
35 (74.47)
151 (67.11)
Widowed
21 (11.80)
6 (12.77)
27 (12.00)
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Country
Age at baseline (years)
KPS at baseline
Gender
Education level
Employment status
Cohabitants
Married status
BM: Bone metastases; BN: Brain metastases; KPS: Karnofsky performance status; SD: Standard deviation.
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Cramarossa, Zeng, Zhang et al.
Table 1. Patient characteristics (cont.). Socio-demographic data
BM: n = 400 (n; %)
BN: n = 47 (n; %)
Total: n = 447 (n; %)
Single
15(8.43)
5(10.64)
20(8.89)
Other
26 (14.60)
1 (2.13)
27 (12.00)
Breast
273 (68.25)
16 (34.04)
289 (64.65)
Lung
31 (7.75)
17 (36.17)
48 (10.74)
Prostate
46 (11.50)
0 (0.00)
46 (10.29)
Gastrointestinal
10 (2.50)
6 (12.77)
16 (3.58)
Renal cell
9 (2.25)
2 (4.26)
11 (2.46)
Others
31 (7.75)
6 (12.77)
37 (8.28)
Outpatient
367 (91.98)
40 (85.11)
407 (91.26)
Inpatient
32 (8.02)
7 (14.89)
39 (8.74)
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Married status (cont.)
Baseline clinical data Primary cancer site
Patients status
BM: Bone metastases; BN: Brain metastases; KPS: Karnofsky performance status; SD: Standard deviation.
patient reported QoL (as assessed by item 30). Multivariate linear regression analysis also revealed no significant relationship with question 30. At follow-up in 30 patients, both univariate and multivariate analysis did not result in any significant predictors. Total patient sample:– overall health
All domain scores except for diarrhea were significantly associated with the overall health item. Multivariate analysis revealed role functioning (p < 0.0001), fatigue (p < 0.0001) and nausea/vomiting (p = 0.0002) as most predictive of overall health (TABLE 3). Fatigue had the largest absolute value coefficient (-0.093), followed by role functioning (0.078) and nausea/vomiting (-0.043). At the 1 month follow-up, univariate analysis revealed all domain scores except constipation and diarrhea were significantly correlated to patient reported overall health. Social functioning (coefficient of 0.077), fatigue (-0.062) and pain (-0.051) remained statistically significant after multivariate analysis. Bone metastases subgroup: overall health
All domain scores except diarrhea were significantly related to overall health. Multivariate analysis identified role functioning (p < 0.0001), fatigue (p < 0.0001) and nausea/vomiting (p < 0.0001) were the most significant predictors of patient reported overall health in this subgroup. Fatigue had the largest absolute value coefficient (-0.090), followed by role functioning (0.087), and nausea/vomiting (-0.050). Univariate analysis at follow-up revealed all domains except insomnia, constipation and diarrhea were statistically significant. Multivariate linear regression analysis revealed that social functioning (coefficient 142
0.081), fatigue (-0.060) and pain (-0.055) remained statistically significant. Brain metastases subgroup: overall health
At baseline, only fatigue significantly associated with patient reported overall health (as assessed by item 29). Multivariate analysis also revealed fatigue as a significant predictor (p = 0.0011; coefficient -0.100). At follow-up, both univariate and multivariate linear regression analysis did not result in any significant predictors in the BN subgroup. Total patient sample: global health status
All domain scores except for diarrhea were significantly associated with the global health status items. Multivariate analysis revealed role functioning (p < 0.0001), fatigue (p = 0.0002) and financial problems (p = 0.0005) as most predictive of global health status (TABLE 4). Role functioning had the largest absolute value coefficient (0.171), followed by fatigue (-0.143), and financial problems (-0.071). At the 1 month follow-up, univariate analysis revealed all domain scores except insomnia, constipation and diarrhea were significantly correlated to global health status. Social functioning (coefficient of 0.197), pain (-0.087) and dyspnea (-0.052) remained statistically significant after multivariate analysis. Bone metastases subgroup: global health status
All domain scores except diarrhea were significantly related to global health status (as assessed by items 29 and 30). Multivariate analysis identified role functioning (p < 0.0001), nausea/ vomiting (p = 0.0001) and financial problems (p = 0.0001) were the most significant predictors of global health status. Expert Rev. Pharmacoecon. Outcomes Res. 14(1), (2014)
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Predictive values for QoL in patients with bone metastases
Role functioning had the largest absolute value coefficient (0.216), followed by and nausea/vomiting (-0.095) and financial problems (-0.085). Univariate analysis at follow-up revealed all domains except insomnia, constipation and diarrhea were statistically significant. Multivariate analysis revealed that social functioning (coefficient 0.212) and pain (-0.104) remained statistically significant. Brain metastases subgroup: global health status
At baseline, no domains were significantly associated with global health status (as assessed by item 29 and 30). Multivariate analysis also revealed no significant relationship with global health status. At follow-up, both univariate and multivariate linear regression analysis did not result in any significant predictors. Discussion
Patient reported QoL as part of the EORTC QLQ-C30 is influenced by a number of other symptoms assessed by the same tool. Palliative patient care may benefit from paying special attention to management of the most significant predictors of QoL, including those identified in the present study and in the literature. The present study analyzed predictive factors in the total patient sample as well in BM and BN subgroups with varying primary cancers. The deterioration of domain/symptom scores may vary in different patient subgroups, evidenced by the dissimilarity in BM and BN subgroup results. This is the first known study to simultaneously analyze predictors of QoL, overall health and global health status to determine if predictive factors are constant regardless of the item used for correlation analysis. Results indicate that there are similar predictors among the three. For the total patient sample at baseline, role functioning and fatigue were significant predictors of QoL, overall health and global health status. At follow-up, social functioning was also a significant predictor for all three items. For the BM subgroup, role functioning was a significant predictor for all three items at baseline, and at follow-up social functioning significantly correlated with QoL, overall health and global health status. These similarities indicate that regardless of the item utilized for correlation analysis, many of the same domains affect cancer patients’ overall condition. There are a few published studies which have conducted similar analyses to determine which domains significantly correlate with the QoL question of the EORTC QLQ-C30. Beijer et al. published a study on pre-terminal cancer patients which found that of the QLQ-C30 domains, fatigue, role functioning, physical functioning, social functioning, nausea, cognitive functioning, appetite loss, dyspnea and emotional functioning had the strongest correlation to QoL with univariate analysis [12]. Multivariate analysis revealed fatigue and social functioning were the major contributors to QoL. In the current study, fatigue was highly significant with overall QoL, health and global health status in the total patient sample at baseline, and social functioning was significant with QoL at baseline and follow-up in the total patient sample. Social functioning www.expert-reviews.com
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Table 2. Multivariate linear regression analysis of most predictive factors of patient reported QoL (question 30) in the total patient sample at baseline. Domain†
Coefficient
SE
p-value
Intercept = 1.282 (SE 0.117), MSE = 0.157 Role functioning
0.061
0.015
