Determination of Cutpoints for Low and High Number of Symptoms in Patients with Advanced Cancer

Article (PDF Available)inJournal of palliative medicine 15(9):1027-36 · August 2012with45 Reads
DOI: 10.1089/jpm.2012.0045 · Source: PubMed
Abstract
Abstract While patients with advanced cancer experience a wide range of symptoms, no work has been done to determine an optimal cutpoint for a low versus a high number of symptoms. Analytic approaches that established clinically meaningful cutpoints for the severity of cancer pain and fatigue provided the foundation for this study. The purpose of this study was to determine the optimal cutpoint for low and high numbers of symptoms using a range of potential cutpoints and to determine if those cutpoints distinguished between the two symptom groups on demographic and clinical characteristics and depression, anxiety, and quality of life (QOL). Patients with advanced cancer (n=110) completed a symptom assessment scale, and measures of depression, anxiety, and QOL. Combinations of cutpoints were tested to yield one- and two-cutpoint solutions. Using analysis of variance for QOL scores, the F-ratio that indicated the highest between-group difference was determined to be the optimal cutpoint between low and high number of symptoms. A cutpoint of ≤12 symptoms (i.e., 0-12 is low, 13-32 is high) was the optimal cutpoint for total number of symptoms. Significant differences in depression, anxiety, and QOL scores validated this cutpoint. Psychological symptoms had higher occurrence rates in the high symptom group. Findings suggest that a threshold exists between a low and a high number of symptoms in patients with advanced cancer. Psychological symptoms were significantly different between patients in the low versus high symptom groups and may play an important role in QOL outcomes in patients with advanced cancer.

Figures

Determination of Cutpoints for Low and High Number
of Symptoms in Patients with Advanced Cancer
Stephanie Gilbertson-White, R.N., Ph.D.,
1
Bradley E. Aouizerat, Ph.D., M.A.S.,
1
Thierry Jahan, M.D.,
2
Steven M. Paul, Ph.D., Claudia West, R.N., M.S.,
1
Karen Schumacher, R.N., Ph.D.,
3
Marylin J. Dodd , R.N., Ph.D.,
1
Michael Rabow, M.D.,
2
Ahmad H. Abu Raddaha, R.N., M.S.N., Ph.D.,
1
and Christine Miaskowski, R.N., Ph.D., FAAN
1
Abstract
While patients with advanced cancer experience a wide range of symptoms, no work has been done to deter-
mine an optimal cutpoint for a low versus a high number of symptoms. Analytic approaches that established
clinically meaningful cutpoints for the severity of cancer pain and fatigue provided the foundation for this study.
The purpose of this study was to determine the optimal cutpoint for low and high numbers of symptoms using a
range of potential cutpoints and to determine if those cutpoints distinguished between the two symptom groups
on demographic and clinical characteristics and depression, anxiety, and quality of life (QOL). Patients with
advanced cancer (n = 110) completed a symptom assessment scale, and measures of depression, anxiety, and
QOL. Combinations of cutpoints were tested to yield one- and two-cutpoint solutions. Using analysis of variance
for QOL scores, the F-ratio that indicated the highest between-group difference was determined to be the
optimal cutpoint between low and high number of symptoms. A cutpoint of £ 12 symptoms (i.e., 0–12 is low,
13–32 is high) was the optimal cutpoint for total number of symptoms. Significant differences in depression,
anxiety, and QOL scores validated this cutpoint. Psychological symptoms had higher occurrence rates in the
high symptom group. Findings suggest that a threshold exists between a low and a high number of symptoms in
patients with advanced cancer. Psychological symptoms were significantly different between patients in the low
versus high symptom groups and may play an important role in QOL outcomes in patients with advanced
cancer.
Introduction
S
erlin and colleagues provided evidence to support the
establishment of clinically meaningful cutpoints for mild,
moderate, and severe pain in oncology patients.
1
Since 1995,
several studies refined these cutpoints for acute,
2,3
chronic,
4
and cancer
5
pain and established cutpoints for cancer-related
fatigue.
6
Cutpoints were created based on the idea that within
the symptom experience, symptom severity comprised the
internal sensory dimension and interference caused by
symptoms comprised the external reactive dimension.
1
The
nonlinear relationship between severity and interference with
function was demonstrated by a statistically significant
‘jump’’ in interference scores as symptom severity went from
mild to moderate or moderate to severe.
1–5
Clinically meaningful cutpoints have served as a founda-
tion for treatment guidelines. For example, the National
Comprehesive Cancer Network used these cutpoints to es-
tablish treatment algorithms for cancer pain
7
and fatigue
management.
8
In addition, cutpoints can be used to determine
if management strategies are effective.
7
Findings from recent reviews suggest that patients with
advanced cancer experience numerous concurrent symp-
toms.
9,10
Across 46 studies, 24 different symptoms occurred
in 20% of the pooled samples. While total number of
symptoms was not examined as a factor that contributes to
significant decrements in quality of life (QOL), various com-
ponents of this concept of symptom burden
11,12
(e.g., symp-
tom severity
13,14
and symptom distress
15,16
) were associated
with significant decreases in functional status and QOL. In
addition, symptom assessment is a clinically meaningful
proxy for QOL and an extremely reliable patient reported
outcome.
11,17
Therefore, it is reasonable to suggest that QOL
could be used as an outcome to evaluate clinically meaningful
Schools of
1
Nursing and
2
Medicine, University of California, San Francisco, California.
3
College of Nursing, University of Nebraska Medical Center, Omaha, Nebraska.
Accepted April 25, 2012.
JOURNAL OF PALLIATIVE MEDICINE
Volume 15, Number 9, 2012
ª Mary Ann Liebert, Inc.
DOI: 10.1089/jpm.2012.0045
1027
cutpoints for low and high number of symptoms in patients
with advanced cancer. In addition, given that patients with
advanced cancer report more symptoms than patients with
earlier-stage disease,
9,18
and comprehensive, multidimen-
sional symptom assessment tools may be burdensome for
patients and clinicians, the determination of a cutpoint for
number of symptoms might have some clinical utility. Rou-
tine screening with a symptom checklist could determine a
patient’s total number of symptoms. Then clinicians could use
a low/high cutpoint to identify high-risk patients who war-
rant more-in-depth assessments and/or more-aggressive
symptom management interventions.
Expanding on Serlin and colleagues’ idea,
1
in this study
total number of symptoms was viewed as the sensory di-
mension of the symptom experience, and QOL was viewed as
the reactive dimension. If total number of symptoms has a
nonlinear relationship with QOL (as does pain severity and
interference), then a significant jump in QOL scores would
occur as the total number of symptoms goes from low to high.
Said another way, clinically meaningful differences in total
number of symptoms would be associated with significant
differences in QOL. This hypothesis is supported by clinical
observations in which patients with advanced cancer manage
relatively well with a ‘‘low’ number of symptoms. However,
when the total number of symptoms crosses some threshold
between low and high, various QOL domains are impaired
and symptom management interventions are not effective.
Therefore, the purposes of this study, in a sample of patients
with advanced cancer, were to determine the optimal cutpoint
for low and high number of symptoms using a range of po-
tential cutpoints and to determine if those cutpoints distin-
guished between the symptom groups in any demographic
and clinical characteristics as well as in depression, anxiety,
and QOL.
Methods
Design and sample
This descriptive study of 110 patients is part of an ongoing
randomized clinical trial that will determine the efficacy of
two different doses of a psychoeducational intervention to
improve cancer pain management. Patients were included if
they: were adult oncology outpatients ( 18 years of age)
experiencing cancer pain of somatic or visceral origin; were
able to read, write, and understand English; agreed to par-
ticipate and provided written informed consent; had a Kar-
nofsky Performance Status (KPS) score of 50; had an
average pain intensity score of 3.0ona0to10numeric
rating scale (NRS); had a life expectancy of 6months;and
had a telephone line. Patients were excluded if they: had
neuropathic cancer pain; had a documented previous or
current psychiatric disorder; or were receiving hospice care,
in order not to interfere with the pain management program
provided by hospice.
Settings
Patients were recruited from a comprehensive cancer cen-
ter, two veterans’ affairs hospitals, and four community-
based oncology clinics. They were asked by a clinician at the
site about study participation. If the patient was interested,
the clinician informed the research nurse, who discussed the
study and obtained written informed consent. Questionnaires
were completed in patients’ homes prior to the onset of the
intervention.
Instruments
The Patient Information Questionnaire obtained demo-
graphic characteristics and KPS score.
19,20
The valid and re-
liable Self-Administered Comorbidity Questionnaire (SCQ),
with scores that range from 0 to 39, provided information on
comorbidities.
21,22
Medical records were reviewed to obtain
information on cancer diagnosis, current treatments, reason
for current treatments, and metastatic sites.
The Memorial Symptom Assessment Scale (MSAS) con-
tains a list of 32 physical and psychological symptoms that
occur as a result of cancer or its treatment. Patients were asked
to indicate whether they had experienced each symptom in
the past week (i.e., symptom occurrence). If they had experi-
enced the symptom, they were asked to rate its frequency of
occurrence, severity, and distress. MSAS was developed for
use with oncology patients
23,24
and has established validity in
palliative care patients.
25
Multidimensional Quality of Life Scale–Cancer Version 2
(MQOLS-CA2) is a 33-item instrument that measures five
dimensions of QOL (i.e., psychological well-being, general
physical well-being, nutrition, symptom distress, and inter-
personal well-being).
26,27
Each item is rated on a 0 to 10 NRS
Table 1. Results of the Cutpoint Analyses for Total
Number of Symptoms Using the Total and Subscale
Scores from the Multidimensional Quality
of Life Scale–Cancer Version 2
Analysis
of variance
Multivariate
analysis of variance
Cutpoints for number
of symptoms per group Rank F Rank F
Low 0–5
High 6–32
10 3.385 12 1.384
Low 0–6
High 7–32
8 6.986 11 2.349
Low 0–7
High 8–32
11 2.696 4 4.479
Low 0–8
High 9–32
12 1.324 9 3.475
Low 0–9
High 10–32
7 9.196 5 4.478
Low 0–10
High 11–32
6 9.401 7 4.053
Low 0–11
High 12–32
9 5.716 10 3.439
Low 0–12
High 13–32
1 13.548 1 5.176
Low 0–13
High 14–32
5 9.815 8 3.752
Low 0–14
High 15–32
3 11.543 3 4.524
Low 0–15
High 16–32
2 11.831 2 4.893
Low 0–16
High 17–32
4 10.360 6 4.277
1028 GILBERTSON-WHITE ET AL.
with higher scores indicating a better QOL. MQOLS-CA2 has
well established validity and reliability.
26,27
Measures used to validate cutpoints
The Center for Epidemiologic Studies–Depression (CES-D)
scale consists of 20 items selected to represent the major
symptoms in the clinical syndrome of depression. Higher
scores indicate higher levels of depression. CES-D has well
established concurrent and construct validity.
28,29
Spielberger State–Trait Anxiety Inventories (STAI-S and
STAI-T) each consist of 20 items. Scores can range from 20 to
80. Higher scores indicate greater anxiety. STAI-T measures
an individual’s predisposition to anxiety determined by his or
her personality and estimates how a person generally feels.
STAI-S measures an individual’s transitory emotional re-
sponse to a stressful situation. Both inventories have well
established validity and reliability.
30,31
The Medical Outcomes Study–Short Form (MOS-SF36), a 36-
item instrument, is a generic measure of QOL. It consists of eight
Table 2. Differences in Demographic and Clinical Characteristics
between the Low (n = 43) and High (n = 67) Total Number of Symptom Groups
Low symptom group High symptom group
n = 43 n = 67
Characteristic Mean (SD) Mean (SD)
Statistics
t-test; p-value
Age (years) 63.6 (10.1) 57.4 (13.1) 2.7; .009
Education (years) 15.5 (3.2) 15.6 (2.5) - 0.02; .985
KPS score 72.9 (12.9) 68.2 (11.5) 1.89; .06
Total number of symptoms 9.7 (2.0) 17.8 (4.0) - 14.10; < .0001
SCQ score 8.0 (3.7) 8.9 (3.7) - 1.20; .235
Number of metastatic sites 1.7 (1.8) 1.8 (1.2) - .325; .746
%(n)%(n) Fisher’s exact test
Male gender 55.8 (24) 40.3 (27) .122
Lives alone 34.9 (15) 13.6 (9) .017
White 81.4 (35) 71.9 (46) .358
Married/partnered 62.8 (27) 67.2 (43) .684
Not employed 76.7 (33) 74.6 (50) 1.000
Cancer diagnosis*
Breast 34.9 (15) 35.8 (24) 1.000
Colon 0.0 (0) 3.0 (2) .519
Lung 9.3 (4) 9.0 (6) 1.000
Melanoma 2.3 (1) 1.5 (1) 1.000
Prostate 23.3 (10) 25.4 (17) 1.000
Leukemia 0.0 (0) 1.5 (1) 1.000
Non-Hodgkin’s lymphoma 0.0 (0) 1.5 (1) 1.000
Ovarian 0.0 (0) 3.0 (2) .519
Other 32.6 (14) 28.4 (19) .674
Two primary cancers 2.3 (1) 9.0 (6) .243
Current treatments*
Radiation therapy 7.1 (3) 9.0 (6) 1.000
Chemotherapy 61.9 (26) 49.3 (33) 2.38
Biotherapy 4.8 (2) 13.4 (9) 1.98
Hormonal therapy 35.7 (15) 31.3 (21) .679
Number of cancer treatments
0 treatments 16.7 (7) 17.9 (12)
Kendall’s tau =-.057; .538
1 treatment 57.1 (24) 62.7 (42)
2 treatments 26.2 (11) 17.9 (12)
3 treatments 0.0 (0) 1.5 (1)
Metastatic sites
0 9.3 (4) 10.4 (7)
Kendall’s tau = .030; .724
1 39.5 (17) 35.8 (24)
2 32.6 (14) 28.4 (19)
3 7.0 (3) 16.4 (11)
4 9.3 (4) 4.5 (3)
5 2.3 (1) 4.5 (3)
Reason for current treatment
Cure 0.0 (0) 3.6 (2)
v
2
= 1.49; .475
Control 81.6 (31) 76.4 (42)
Palliation 18.4 (7) 20.0 (11)
KPS, Karnofsky Performance Status; SCQ, Self-administered Comorbidity Questionnaire; SD, Standard deviation.
*Percentage totals exceed 100% because patients may have more than one type of cancer or treatment.
CUTPOINTS FOR LOW AND HIGH NUMBERS OF SYMPTOMS 1029
subscales and two component scores that evaluate important
health concepts. Higher scores indicate better QOL.
32,33
Data analysis
Data were analyzed using SPSS 18.0 (SPSS Inc., Chicago,
IL). Descriptive statistics were used to characterize the sample
and the study variables. Symptom occurrence rates were
generated for each of the symptoms evaluated on the MSAS.
Total number of symptoms was calculated by summing
the number of symptoms based on a response on any one of
the four dimensions—occurrence, frequency, severity, and
distress.
A cutpoint that divided the sample into low and high
number of symptoms was created using the analytic strategy
of Serlin and colleagues.
1
Twelve categorical variables that
represented dichotomizing the number of symptoms into low
and high using the twelve possible cutpoints between 5 and
16 were created (e.g., 0–5 = low, 6–32 = high, 0–6 = low, 7–
32 = high, and so on up to 0–16 = low, 17–32 = high) and re-
lated to the five MQOLS-CA2 subscales using multivariate
analysis of variance (MANOVA) and to the MQOLS-CA2
total score using analysis of variance (ANOVA). Combina-
tions of cutpoints were tested to yield two cutpoints (three
groups) as well as one cutpoint (two groups) solutions. The
criterion used to determine the optimal cutpoint groups
was the F-ratio for the between-group effect for both the
MANOVA and the ANOVA (Table 1). While attempts were
made to establish cutpoints for low, medium, and high total
number of symptoms, a clear cutpoint between medium and
high was not identified. Therefore, the analysis proceeded to
determine a single cutpoint solution. Five symptoms was
selected as the lower limit and 16 symptoms as the upper limit
of testable cutpoints, because no patient reported fewer than
5 symptoms, and 16 symptoms was approximately equal to
the mean number of symptoms for the sample.
To determine if the optimal cutpoint for the total number of
symptoms differed between the low and high symptom
groups on demographic and clinical characteristics, inde-
pendent sample t-tests and v
2
and Kendall’s tau analyses were
used. Preliminary analyses revealed significant between-
groups differences for age and living arrangements. Because
only age is associated with depression,
34,35
anxiety
36
and/or
QOL
37,38
analyses of covariance (ANCOVA), controlling for
age, were used to evaluate for between-group differences in
these measures. All calculations used actual values. Adjust-
ments were not made for missing data. Therefore, the cohort
for each analysis was dependent on the largest set of complete
data between the groups. A p-value of < 0.05 was considered
statistically significant.
Table 3. Differences in the Rank Order of Symptom Occurrence Rates in the Low and High Symptom Groups
Low symptom group (n = 43) High symptom group (n = 67)
Rank Symptom
Occurrence
rate % Symptom
Occurrence
rate %
1 Pain 97.6 Lack of energy 97.0
2 Lack of energy 92.7 Pain 96.9
3 Feeling drowsy 73.2 Feeling sad 90.9
4 Difficulty sleeping 58.5 Feeling drowsy 89.4
5 Constipation 51.2 Worrying 84.6
6 Numbness/tingling in hands/feet 48.8 Difficulty concentrating 81.8
7 Lack of appetite 45.2 Difficulty sleeping 81.8
8 Worrying 42.9 Lack of appetite 77.3
8 Feeling sad 42.9 Feeling irritable 76.1
10 Difficulty concentrating 39.0 Feeling nervous 72.3
11 Change in the way food tastes 37.2 Constipation 68.2
12 Dry mouth 36.6 Nausea 66.7
13 Problems with sexual interest or activity 28.2 Problems with sexual interest or activity 60.7
14 Feeling irritable 27.9 Dry mouth 60.6
15 Nausea 24.4 Numbness/tingling in hands/feet 60.0
16 Itching 21.4 Itching 57.6
17 Dizziness 20.9 Sweats 56.9
18 Cough 19.5 ‘I don’t look like myself’ 48.5
19 Sweats 19.0 Feeling bloated 47.7
19 Problems with urination 19.0 Changes in skin 46.3
19 Feeling bloated 19.0 Change in the way food tastes 44.8
22 Weight loss 18.6 Dizziness 44.8
23 Feeling nervous 17.1 Shortness of breath 40.9
24 Shortness of breath 16.7 Cough 38.5
24 Diarrhea 16.7 Swelling of arms or legs 37.3
26 Vomiting 14.3 Weight loss 37.3
26 Swelling of arms or legs 14.3 Hair loss 31.3
28 Hair loss 11.6 Vomiting 27.3
29 ‘I don’t look like myself’ 9.5 Difficulty swallowing 26.9
30 Mouth sores 9.3 Problems with urination 24.6
31 Difficulty swallowing 7.1 Diarrhea 22.7
31 Changes in skin 7.1 Mouth sores 19.7
1030 GILBERTSON-WHITE ET AL.
Results
Cutpoint calculations
As shown in Table 1, a cutpoint of £ 12 symptoms (i.e.,
0–12 symptoms is low and 13–32 symptoms is high) was
the optimal cutpoint, in that it had the largest between-
group F-ratios for both the MQOLS-CA2 subscale and total
scores. Using £ 12 symptoms as the cutpoint, 60.9% of the
sample (n = 67) was classified as having a high number of
symptoms.
Differences in demographic
and clinical characteristics
Consistent with the American Cancer Society’s definition
of advanced cancer,
39
the majority of the patients had met-
astatic disease (*90%) and their goals of treatment were
control or palliation (*96%). Except for age and living ar-
rangements, no differences were found between the low
and high symptom groups in any demographic or clini-
cal characteristics (Table 2). Patients in the high symptom
FIG. 1A. Differences in Center for Epidemiologic Studies–Depression (CES-D) subscale and total scores between patients in
the low (n = 43) and high (n = 67) symptom groups.
FIG. 1B. Differences in Spielberger State–Trait Anxiety Inventories (STAI) scores between patients in the low (n = 43) and
high (n = 67) symptom groups. All values are plotted as means standard error of the means after controlling for age ( p
values, * < .05, ** £ .001,
+
< .0001).
CUTPOINTS FOR LOW AND HIGH NUMBERS OF SYMPTOMS 1031
group were significantly younger and were less likely to live
alone.
Differences in symptom occurrence rates
As shown in Table 3, differences were found in the occur-
rence rates and rank order of the various MSAS symptoms.
Pain, lack of energy, feeling drowsy, difficulty sleeping, con-
stipation, lack of appetite, worrying, feeling sad, and diffi-
culty concentrating ranked within the top 12 for both the low
and high symptom groups. Numbness/tingling in hands/
feet, changes in the way food tastes, and dry mouth were
among the top 12 symptoms for the low but not for the high
symptom group. In contrast, feeling nervous, feeling irritable,
and nausea were in the top 12 for the high but not for the low
symptom group. Of note, all four of the psychological
symptoms (i.e., feeling sad, worrying, feeling nervous, feeling
irritable) were among the top 12 symptoms in the high
symptom group.
With regard to occurrence rates, pain and lack of energy
had similar occurrence rates in both symptom groups. For the
low symptom group, occurrence rates for the next ten
symptoms ranged from as high as 73.2% for feeling drowsy
to 36.6% for dry mouth. For the high symptom group, the next
10 highest ranked symptoms had much higher occurrence
rates (i.e., 90.9% for feeling sad to 66.7% for nausea).
FIG. 2A. Differences in Multidimensional Quality of Life Scale–Cancer 2 (MQOLS-CA2) subscale and total quality of life
(QOL) scores between patients in the low (n = 43) and high (n = 67) symptom groups.
FIG. 2B. Differences in Medical Outcomes Study–Short Form 36 (MOS-SF36) subscale (PF = physical functioning, RP = role
limitations–physical, BP = bodily pain, GH = general health, V = vitality, SF = social functioning, RE = role limitations–emo-
tional, MH = mental health) and component (PCS = physical component score, MCS = mental component score) scores be-
tween patients in the low (n = 43) and high (n = 67) symptom groups. All values are plotted as means standard error of the
means after controlling for age ( p values, * < .05, .** £ .01,
+
< .0001).
1032 GILBERTSON-WHITE ET AL.
Differences in depression and anxiety scores
After controlling for age, significant between-group dif-
ferences were found in two of the four CES-D subscales (so-
matic and depressed affect) as well as in the total CES-D score
(Figure 1A). Patients in the high symptom group reported a
higher somatic and depressed affect subscale scores as well as
total CES-D score.
After controlling for age, significant between-group dif-
ferences were found in both anxiety scores (Figure 1B). Pa-
tients in the high symptom group reported significantly
higher state and trait anxiety scores.
Differences in QOL scores
As expected, after controlling for age, significant between-
group differences were found in the total MQOLS-CA2
score as well as in four of the five MQOLS-CA2 subscale
(physical, nutrition, symptom distress, and psychological)
scores (Figure 2A). Patients in the high symptom group had
lower subscale and total MQOLS-CA2 scores.
After controlling for age, significant between-group dif-
ferences were found for seven of eight MOS-SF36 subscale
scores (physical functioning, bodily pain, general health, vi-
tality, social functioning, role limitations–emotional, and
mental health), as well as in the mental component score
(Figure 2B). Patients in the high symptom group reported
significantly lower MOS-SF36 scores.
Discussion
This study is the first to determine the optimal cutpoint for
total number of symptoms in patients with advanced cancer.
This finding suggests that the concept of a clinically mean-
ingful cutpoint for symptom severity scores is transferable to
total number of symptoms. In this sample, the cutpoint of 12
symptoms successfully differentiated between patients with
advanced cancer based on a significant jump in both MQOL-
CA2 subscale and total scores.
Validation of 12 symptoms as the optimal cutpoint was
supported by significant between-group differences in de-
pression and anxiety scores and in a generic measure of QOL.
As shown in Table 4, between-group differences in these scores
equate with medium to large effect sizes.
40
Previous research
suggests that an effect size of 0.2 to 0.5 is considered a mini-
mally important difference and a clinically meaningful differ-
ence in QOL measures.
41–43
Cinical significance goes beyond
statistical significance to identify whether a change is large
enough to be noticed by the patient.
44–47
Our findings suggest
that when a patient crosses the threshold from 12 to 13 symp-
toms he or she may notice a decrease in various aspects of QOL.
MQOLS-CA2 total scores in this study were similar to those
reported in previous studies of oncology patients.
48,49
Overall,
patients with advanced cancer appear to have moderate dec-
rements in QOL. However, further research is needed to de-
termine the generalizability of these findings and whether
response shifts occur in evaluations of QOL in these patients.
50,51
The cutpoint that differentiated between low and high
number of symptoms was validated by between-group dif-
ferences in the rank order of the psychological symptoms on
the MSAS. All four psychological symptoms (worrying, feel-
ing sad, feeling nervous, feeling irritable) were among the top
12 symptoms in the high symptom group. In contrast, in the
low symptom group, each psychological symptom had a
lower overall rank and occurrence rate, and only worrying
and feeling sad were in the top 12 symptoms.
CES-D scores for the low and high symptom groups in this
study were similar to scores reported by patients with ad-
vanced head and neck cancer.
52,53
In contrast, higher total
CES-D scores were reported by patients with advanced stages
of ovarian
54
and prostate
55
cancer. These inconsistent findings
may be attributed to heterogeneity in cancer diagnoses,
treatment regimens, and timing of assessments.
Mean state and trait anxiety scores in this study are similar
to previous reports of patients with advanced cancer.
56–58
State anxiety increases in response to physical danger and
psychological stress, whereas higher trait anxiety is associated
with diagnoses of psycho-neuroticism and/or depression.
31,59
The consistent levels of anxiety across studies suggest that
patients with advanced cancer may experience acute anxiety
from a variety of physical and emotional stressors as well as
chronic anxiety associated with depressive symptoms.
In this study, mean MOS-SF36 subscale and component
scores for the total sample ranged from 32.1 ( 8.8) for the
physical component score to 64.8 ( 19.8) for the mental
health subscale. These scores are similar to those reported in
one study,
60
lower than scores reported in three studies of
patients with advanced cancer,
61–63
and higher than scores
reported in another study
64
of patients with advanced cancer.
Reasons for these inconsistencies may include differences in
studies’ definition of advanced cancer, their inclusion and
exclusion criteria, and timing of the assessments.
Differences in patients’ reports of symptom occurrence and
the rank order of the most common symptoms support the
between-group differences found for the depression, anxiety,
and psychological/mental health domains of the MOS-SF36.
The largest effect sizes were found for the mental component
and subscale scores related to psychological status (social
functioning, vitality, role limitations–emotional, mental health).
Table 4. Effects Sizes for Between-Group Differences
(High-Low) in Subscale and Total Scores
for the Validation Scales for Depression,
Anxiety, and Quality of Life
Instrument Effect size
Center for Epidemiologic Study–Depression (CES-D) Scale
Somatic .70
Depressed affect .42
Positive affect - .32
Interpersonal .04
Total CES-D score .58
Spielberger State–Trait Anxiety Inventories
Trait anxiety score .59
State anxiety score .64
Medical Outcomes Study–Short Form 36
Physical functioning - .50
Role limitations, physical - .26
Bodily pain - .46
General health - .41
Vitality - .62
Social functioning - .57
Role limitations, emotional - .68
Mental health - .71
Physical component score - .17
Mental component score - .75
CUTPOINTS FOR LOW AND HIGH NUMBERS OF SYMPTOMS 1033
Emerging evidence suggests that psychological symptoms
contribute to decrements in QOL in patients with advanced
cancer.
65–68
For example, higher depression scores were as-
sociated with higher symptom severity scores.
69
In addition,
in a study of cancer patients in their last year of life,
68
higher
levels of depressive symptoms at enrollment were associated
with a worse symptom experience over time. It is not clear if
psychological symptoms result in more symptoms or if length
of time since diagnosis produces psychological ‘wear and
tear’ that results in more psychological and physical symp-
toms. Furthermore, it is not known if psychological and ex-
istential distress increase in patients with advanced cancer as
they approach the end of life.
70
Several study limitations need to be acknowledged. In this
relatively small sample, only one optimal cutpoint for total
number of symptoms was found. However, studies with
larger samples may identify additional cutpoints. The fairly
homogeneous sample of white and well-educated adults, all
of whom had pain, limits the generalizability of the findings.
However, given that pain was a highly prevalent symptom in
both symptom groups, it is unlikely that the results of this
study could be attributed only to pain. Finally, it is not pos-
sible to separate the effects of cancer and its treatment (e.g.,
side effects of medications) and the effects of chronic medical
conditions on the patients’ symptom experience.
Study findings suggest that a threshold exists between low
and high number of symptoms in patients with advanced
cancer. Additional research is needed to confirm these results
and determine if additional cutpoints can be identified. In
addition, studies need to determine if the use of cutpoints for
total number of symptoms leads to improvements in clinical
assessments and more tailored interventions for this vulner-
able population. With the movement in health care toward
systematizing best practices in an efficient manner, a need
exists to develop screening criteria which, even if automated,
would assure that the maximum number of patients who are
at greatest risk for worse symptom outcomes are recognized
with the minimum amount of effort. In the meantime, clini-
cians can administer a symptom checklist like the MSAS on a
routine basis. Patients who report the occurrence of 13
symptoms warrant more detailed evaluation and more ag-
gressive symptom management.
Acknowledgments
This work was supported by a grant (CA 116423) from the
National Cancer Institute and the National Institute of Nur-
sing Research. Dr. Miaskowski receives support from the
American Cancer Society as a Clinical Research Professor. Dr.
Aouizerat was funded through National Institutes of Health
Roadmap for Medical Research Grant KL2 RR624130. The
authors gratefully acknowledge the patients and family
caregivers who participated in this research and our many
colleagues who assisted with participant recruitment.
Author Disclosure Statement
No conflicting financial interests exist.
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Address correspondence to:
Christine Miaskowski, R.N., Ph.D., FAAN
Department of Physiological Nursing
University of California
2 Koret Way, Box 0610
San Francisco, CA 94143-0610
E-mail: chris.miaskowski@nursing.uscf.edu
1036 GILBERTSON-WHITE ET AL.

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