World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website http://www.wjon.org

Original Article

Volume 3, Number 1, February 2012, pages 23-32

Symptom Clusters Using the Edmonton Symptom Assessment System in Patients With Bone Metastases: A Reanalysis Comparing Different Statistical Methods

Figure 1. PROC TREE procedure generated dendrogram displaying three cluster solution and cluster hierarchy. More similar symptoms were joined together earlier.

**Table 1.** Patient Characteristics
Characteristics	N (%)
SD: standard deviation.
Age at radiation (year)
Mean ± SD	67.9 ± 10.9
Median (range)	68 (31 - 93)
Sex
Male	280 (54%)
Female	238 (46%)
Weight loss ≥ 10% in the past 6 months
No	261 (50%)
Yes	180 (35%)
Unknown	77 (15%)
Karnofsky Performance Status
Mean ± SD	61.2 ± 14.1
Median (range)	60 (10 - 100)
Total Morphine Equivalent
Mean ± SD	103 ± 234
Median (range)	30 (0 - 3600)
Primary cancer sites
Breast	127 (25%)
Prostate	117 (23%)
Lung	130 (25%)
GI	39 (8%)
Unknown	34 (7%)
Others	71 (14%)

Table 1. Patient Characteristics

Characteristics

N (%)

SD: standard deviation.

Age at radiation (year)

Mean ± SD

67.9 ± 10.9

Median (range)

68 (31 - 93)

Sex

Male

280 (54%)

Female

238 (46%)

Weight loss ≥ 10% in the past 6 months

261 (50%)

Yes

180 (35%)

Unknown

77 (15%)

Karnofsky Performance Status

Mean ± SD

61.2 ± 14.1

Median (range)

60 (10 - 100)

Total Morphine Equivalent

Mean ± SD

103 ± 234

Median (range)

30 (0 - 3600)

Primary cancer sites

Breast

127 (25%)

Prostate

117 (23%)

Lung

130 (25%)

39 (8%)

Unknown

34 (7%)

Others

71 (14%)

**Table 2.** Initial Two Symptom Clusters Identified Using Centroid Cluster Algorithm in HCA
	R²
HCA: Hierarchical Component Analysis; First Cluster explained 47%, second Cluster explained 84% of the total variation. The Cluster 1 will be split due to the smallest proportion of variation (47%).
Cluster 1	Pain	0.3863	0.0663	0.6573
	Fatigue	0.5332	0.1531	0.5512
	Nausea	0.4157	0.1303	0.6719
	Drowsiness	0.5374	0.1420	0.5392
	Poor Appetite	0.5290	0.1088	0.5285
	Sense of Well-being	0.5762	0.2457	0.5618
	Shortness of Breath	0.3387	0.0558	0.7004
Cluster 2	Depression	0.8383	0.2745	0.2228
	Anxiety	0.8383	0.1686	0.1944

Table 2. Initial Two Symptom Clusters Identified Using Centroid Cluster Algorithm in HCA

R²

Own Cluster

Next Cluster

1 – R²_{own cluster}

HCA: Hierarchical Component Analysis; First Cluster explained 47%, second Cluster explained 84% of the total variation. The Cluster 1 will be split due to the smallest proportion of variation (47%).

Cluster 1

Pain

0.3863

0.0663

0.6573

Fatigue

0.5332

0.1531

0.5512

Nausea

0.4157

0.1303

0.6719

Drowsiness

0.5374

0.1420

0.5392

Poor Appetite

0.5290

0.1088

0.5285

Sense of Well-being

0.5762

0.2457

0.5618

Shortness of Breath

0.3387

0.0558

0.7004

Cluster 2

Depression

0.8383

0.2745

0.2228

Anxiety

0.8383

0.1686

0.1944

**Table 3.** Final Two Symptom Clusters Determined Using HCA With Centroid Cluster Algorithm
	R²
HCA: Hierarchical Component Analysis. One Cluster 1 explained 44%, two Clusters explained 55%, and three Clusters explained 64% of the total variation
Cluster 1	Pain	0.4842	0.1412	0.6006
	Fatigue	0.6378	0.2182	0.4633
	Drowsiness	0.6305	0.2299	0.4798
	Sense of Well-being	0.6007	0.3140	0.5820
Cluster 2	Depression	0.8383	0.2525	0.2163
	Anxiety	0.8383	0.1655	0.1937
Cluster 3	Nausea	0.5776	0.2012	0.5288
	Poor Appetite	0.6176	0.3123	0.5561
	Shortness of Breath	0.5129	0.1464	0.5706

Table 3. Final Two Symptom Clusters Determined Using HCA With Centroid Cluster Algorithm

R²

Own Cluster

Next Cluster

1 – R²_{own cluster}

HCA: Hierarchical Component Analysis. One Cluster 1 explained 44%, two Clusters explained 55%, and three Clusters explained 64% of the total variation

Cluster 1

Pain

0.4842

0.1412

0.6006

Fatigue

0.6378

0.2182

0.4633

Drowsiness

0.6305

0.2299

0.4798

Sense of Well-being

0.6007

0.3140

0.5820

Cluster 2

Depression

0.8383

0.2525

0.2163

Anxiety

0.8383

0.1655

0.1937

Cluster 3

Nausea

0.5776

0.2012

0.5288

Poor Appetite

0.6176

0.3123

0.5561

Shortness of Breath

0.5129

0.1464

0.5706

**Table 4.** Eigenvalues and Proportions of Variance for the Nine ESAS Items Using EFA
Component	Eigenvalue	Proportion	Cumulative
BPI: Brief Pain Inventory; EFA: Exploratory Factor Analysis. From eigenvalues and proportions of variance, two factors (clusters) were retained (eigenvalue > 1.0 and proportion > 10%), and the cumulative variance showed up to 100%.
1	10.7297	0.8254	0.8254
2	2.2704	0.1746	1.0000
3	0.4049	0.0311	1.0311
4	0.0902	0.0069	1.0381
5	0.0228	0.0018	1.0398
6	0.0027	0.0002	1.0400
7	-0.0714	-0.0055	1.0346
8	-0.1698	-0.0131	1.0215
9	-0.2794	-0.0215	1.0000

Table 4. Eigenvalues and Proportions of Variance for the Nine ESAS Items Using EFA

Component

Eigenvalue

Proportion

Cumulative

BPI: Brief Pain Inventory; EFA: Exploratory Factor Analysis. From eigenvalues and proportions of variance, two factors (clusters) were retained (eigenvalue > 1.0 and proportion > 10%), and the cumulative variance showed up to 100%.

10.7297

0.8254

2.2704

0.1746

1.0000

0.4049

0.0311

1.0311

0.0902

0.0069

1.0381

0.0228

0.0018

1.0398

0.0027

0.0002

1.0400

-0.0714

-0.0055

1.0346

-0.1698

-0.0131

1.0215

-0.2794

-0.0215

1.0000

**Table 5.** Factor Loadings and Final Communality Determined Using EFA
	Factor 1	Factor 2	Final communality
EFA: Exploratory Factor Analysis.
Drowsiness	0.67	0.20	0.49
Fatigue	0.66	0.23	0.49
Sense of Well-being	0.65	0.36	0.55
Poor Appetite	0.63	0.20	0.44
Pain	0.51	0.14	0.28
Nausea	0.49	0.26	0.31
Dyspnea	0.44	0.13	0.21
Depression	0.29	0.89	0.87
Anxiety	0.23	0.69	0.53
% of variance	82.5%	17.5%
Cronbach’s alpha	0.82	0.81

Table 5. Factor Loadings and Final Communality Determined Using EFA

Factor 1

Factor 2

Final communality

EFA: Exploratory Factor Analysis.

Drowsiness

0.67

0.20

0.49

Fatigue

0.66

0.23

0.49

Sense of Well-being

0.65

0.36

0.55

Poor Appetite

0.63

0.20

0.44

Pain

0.51

0.14

0.28

Nausea

0.49

0.26

0.31

Dyspnea

0.44

0.13

0.21

Depression

0.29

0.89

0.87

Anxiety

0.23

0.69

0.53

% of variance

82.5%

17.5%

Cronbach’s alpha

0.82

0.81

**Table 6.** Symptom Clusters Identified at Baseline and Follow-Ups Using Three Statistical Methods
Symptom	Baseline (n = 518)	1 week FU (n = 272)	2 week FU (n = 297)	4 week FU (n = 266)	8 week FU (n = 231)	12 week FU (n = 193)
FU: follow-up; PCA: Principal Component Analysis; EFA: Exploratory Factor Analysis; HCA: Hierarchical Component Analysis. Symptoms with corresponding symbols indicate they were in the same cluster. Dash indicates the symptom was not present in any clusters.
Depression	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	—	Δ	Δ	Δ	Δ
Anxiety	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	—	Δ	Δ	Δ	Δ
Fatigue	Ο	Ο	Ο	Ο	Ο	Ο	O	Ο	Ο	Ο	Ο	Ο	Δ	—	Ο	Ο	Ο	Ο
Drowsiness	Ο	Ο	Ο	Ο	Ο	Ο	O	Ο	Ο	Ο	Ο	Ο	Ο	—	Ο	Ο	Ο	Ο
Pain	O	Ο	O	X	Ο	X	O	Ο	Ο	Δ	Ο	O	Δ	—	Δ	Ο	Ο	Ο
Nausea	X	Ο	X	X	Δ	X	Δ	Δ	Δ	Ο	Ο	Ο	Ο	—	Ο	X	Ο	X
Poor appetite	X	Ο	X	X	Ο	X	Δ	Ο	Δ	Ο	Ο	Ο	Δ	—	Δ	Δ	Ο	Δ
Dyspnea	X	Ο	X	O	Ο	Ο	—	Ο	—	—	Δ	—	—	—	—	X	Ο	X
Poor well-being	O	Ο	O	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	—	Δ	Δ	Δ	Δ

Table 6. Symptom Clusters Identified at Baseline and Follow-Ups Using Three Statistical Methods

Symptom

Baseline (n = 518)

1 week FU (n = 272)

2 week FU (n = 297)

4 week FU (n = 266)

8 week FU (n = 231)

12 week FU (n = 193)

PCA

EFA

HCA

PCA

EFA

HCA

PCA

EFA

HCA

PCA

EFA

HCA

PCA

EFA

HCA

PCA

EFA

HCA

FU: follow-up; PCA: Principal Component Analysis; EFA: Exploratory Factor Analysis; HCA: Hierarchical Component Analysis. Symptoms with corresponding symbols indicate they were in the same cluster. Dash indicates the symptom was not present in any clusters.

Depression

—

Anxiety

—

Fatigue

—

Drowsiness

—

Pain

—

Nausea

—

Poor appetite

—

Dyspnea

—

Poor well-being

—

**Table 7.** Symptom Clusters in Responders Versus Non-Responders Subgroups Using PCA
Method	Symptom	Baseline	1 week FU	2 week FU	4 week FU	8 week FU	12 week FU
PCA: Principal Component Analysis; FU: follow-up; NR: non-responders; R: responders. Symptoms with corresponding symbols indicate they were in the same cluster.
Dash indicates the symptom was not present in any clusters.
	Depression	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ
	Anxiety	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ
	Fatigue	X	X	Ο	Ο	Ο	Δ	Ο	O	Ο	Δ	Ο	Δ
	Drowsiness	X	X	Ο	Ο	Ο	Δ	Ο	O	Ο	Δ	Ο	Δ
PCA	Pain	X	X	X	X	X	Δ	Δ	X	Δ	—	Ο	—
	Nausea	O	O	X	X	Δ	O	Ο	X	Ο	O	X	Δ
	Poor appetite	O	O	X	Ο	Δ	O	X	O	Δ	O	O	O
	Dyspnea	Ο	Ο	Ο	Ο	X	—	X	O	—	O	X	O
	Poor well-being	X	X	Δ	Δ	Δ	O	Δ	Δ	Δ	Δ	Δ	Δ

Table 7. Symptom Clusters in Responders Versus Non-Responders Subgroups Using PCA

Method

Symptom

Baseline

1 week FU

2 week FU

4 week FU

8 week FU

12 week FU

NR
n = 518

R
n = 518

NR
n = 140

R
n = 132

NR
n = 148

R
n = 149

NR
n = 132

R
n = 134

NR
n = 122

R
n = 109

NR
n = 95

R
n = 98

PCA: Principal Component Analysis; FU: follow-up; NR: non-responders; R: responders. Symptoms with corresponding symbols indicate they were in the same cluster.

Dash indicates the symptom was not present in any clusters.

Depression

Anxiety

Fatigue

Drowsiness

PCA

Pain

—

Nausea

Poor appetite

Dyspnea

—

Poor well-being

**Table 8.** Symptom Clusters in Responders Versus Non-Responders Subgroups Using EFA
Method	Symptom	Baseline	1 week FU	2 week FU	4 week FU	8 week FU	12 week FU
EFA: Exploratory Factor Analysis; FU: follow-up; NR: non-responders; R: responders. Symptoms with corresponding symbols indicate they were in the same cluster. Dash indicates the symptom was not present in any clusters.
	Depression	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	—	Δ	Δ
	Anxiety	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	—	Δ	Δ
	Fatigue	Ο	Ο	Ο	Ο	Ο	Ο	Ο	Ο	Ο	—	Ο	Δ
	Drowsiness	Ο	Ο	Ο	Ο	Ο	Ο	Ο	Ο	Ο	—	Ο	O
EFA	Pain	Ο	Ο	X	Δ	Δ	Δ	O	Δ	Δ	—	Ο	Δ
	Nausea	Ο	Ο	X	Δ	Δ	Ο	O	Δ	Ο	—	Ο	O
	Poor appetite	Ο	Ο	X	Ο	Δ	Ο	Δ	O	Δ	—	Ο	Δ
	Dyspnea	Ο	Ο	Ο	Ο	Ο	Δ	Δ	Ο	O	—	Ο	Δ
	Poor well-being	Ο	Ο	Δ	Δ	Δ	Ο	Δ	Δ	Δ	—	—	Δ

Table 8. Symptom Clusters in Responders Versus Non-Responders Subgroups Using EFA

Method

Symptom

Baseline

1 week FU

2 week FU

4 week FU

8 week FU

12 week FU

NR
n = 518

R
n = 518

NR
n = 140

R
n = 132

NR
n = 148

R
n = 149

NR
n = 132

R
n = 134

NR
n = 122

R
n = 109

NR
n = 95

R
n = 98

EFA: Exploratory Factor Analysis; FU: follow-up; NR: non-responders; R: responders. Symptoms with corresponding symbols indicate they were in the same cluster. Dash indicates the symptom was not present in any clusters.

Depression

—

Anxiety

—

Fatigue

—

Drowsiness

—

EFA

Pain

—

Nausea

—

Poor appetite

—

Dyspnea

—

Poor well-being

—

**Table 9.** Symptom Clusters in Responders Versus Non-Responders Subgroups Using HCA
Method	Symptom	Baseline	1 week FU	2 week FU	4 week FU	8 week FU	12 week FU
HCA: Hierarchical Component Analysis; FU: follow-up; NR: non-responders; R: responders. Symptoms with corresponding symbols indicate they were in the same cluster. Dash indicates the symptom was not present in any clusters.
	Depression	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ
	Anxiety	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ	Δ
	Fatigue	X	X	Ο	Ο	Ο	Δ	Ο	Ο	Δ	Δ	Ο	Δ
	Drowsiness	X	X	Ο	Ο	Ο	Δ	Ο	Ο	Δ	Δ	Ο	Ο
HCA	Pain	X	X	X	X	X	Δ	Δ	X	O	—	Ο	X
	Nausea	O	O	X	X	Δ	X	Ο	X	Δ	O	X	O
	Poor appetite	O	O	X	O	—	X	Δ	Ο	O	Δ	O	Ο
	Dyspnea	Ο	Ο	Ο	Ο	X	—	—	O	—	O	X	X
	Poor well-being	X	X	Δ	Δ	Δ	X	Δ	Δ	O	Δ	Δ	Δ

Table 9. Symptom Clusters in Responders Versus Non-Responders Subgroups Using HCA

Method

Symptom

Baseline

1 week FU

2 week FU

4 week FU

8 week FU

12 week FU

NR
n = 518

R
n = 518

NR
n = 140

R
n = 132

NR
n = 148

R
n = 149

NR
n = 132

R
n = 134

NR
n = 122

R
n = 109

NR
n = 95

R
n = 98

HCA: Hierarchical Component Analysis; FU: follow-up; NR: non-responders; R: responders. Symptoms with corresponding symbols indicate they were in the same cluster. Dash indicates the symptom was not present in any clusters.

Depression

Anxiety

Fatigue

Drowsiness

HCA

Pain

—

Nausea

Poor appetite

—

Dyspnea

—

Poor well-being