Research Article
The Evaluation of Dyspnea in Elderly Patients with Advanced Non-Small-Cell-Lung Cancer Receiving Palliative Chemotherapy
Bozena Weryńska, Irena Porębska* and Anna Brzecka
Department of Pulmonology and Lung Cancer, Medical University, Wroclaw, Poland
*Corresponding author: Irena Porębska, Department of Pulmonology and Lung Cancer, Medical University, Wroclaw, Poland
Published: 22 Mar, 2017
Cite this article as: Weryńska B, Porębska I, Brzecka A. The Evaluation of Dyspnea in Elderly Patients with Advanced Non-SmallCell-Lung Cancer Receiving Palliative Chemotherapy. Clin Oncol. 2017; 2: 1241.
Abstract
Background: Therapeutic decisions in lung cancer patients are in great part based on ECOG
performance status. Little is known, however, what is the relation between dyspnea and ECOG
performance status. The aim of the study was to elucidate to what extent dyspnea influences ECOG
performance status in the elderly patients with the with advanced Non-Small Cell Lung Cancer
(NSCLC) and whether dyspnea may be considered as a factor influencing the results of palliative
chemotherapy.
Material and Methods: Material of the study consisted of 27 patients aged over 65 years with
advanced NSCLC scheduled for the first-line palliative chemotherapy. The following studies were
performed: spirometry, Modified Medical Research Council (mMRC) questionnaire, Six Minutes
Walk Test (6MWT), Borg dyspnea scale, and COPD Assessment Test (CAT). After removing from
CAT 3 items not related to dyspnea (cough, phlegm and sleep), the remaining 5 questions were
analyzed as modified CAT, i.e. mCAT.
Results: Dyspnea was a complaint of 78% of patients. The patients with ECOG 1/ECOG 2
performance status had higher mMRC and CAT scores than the patients with ECOG 0 performance
status. mCAT score was almost 2.5 times higher in the patients with ECOG 1/ECOG 2 than in
the patients with ECOG 0 performance status (13.0 ± 5.1 vs. 5.1 ± 5.1, p <0.001). Score of mCAT
positively correlated with the score in mMRC scale (r = 0.68, p <0.05) and Borg scale at rest
(r=0.390, p <0.05) and negatively correlated with the distance in the 6MWT (r = -0.56, p <0.05).
Non-completion of chemotherapy was associated with smaller FEV1 and FVC, shorter distance in
6MWT and more severe dyspnea in the Borg scale.
Conclusion: Dyspnea is a complaint of the majority of elderly patients with advanced NSCLC
patients and is more severe in the patients with the performance status higher than ECOG 0. 6MWT
and modified CAT are the best tools to evaluate dyspnea in the elderly patients with advanced
NSCLC. The evaluation of dyspnea may help to assess the performance status in the elderly patients
with advanced NSCLC. Objective measure of dyspnea, i.e. shortened distance in 6MWT, may allow
to predict unfavorable course of the palliative chemotherapy in the elderly patients with advanced
NSCLC.
Keywords: Lung cancer; Dyspnea; Performance status; CAT; mMRC; Six-minutes-test walk
Introduction
Dyspnea, important problem in the patients with lung cancer, may have multiple causes,
including – among the other – atelectasis, multiple metastases, carcinomatous lymphangiosis,
superior vena cava syndrome, infiltration of mediastinum and paresis of laryngeal and/or phrenic
nerves, pleural or pericardial fluid, secondary pneumonia, thromboembolic lung disease. Dyspnea
in the course of lung cancer, occurs regardless the age and sometimes may be very severe [1-3]. It strongly influences performance status of the patients.
Therapeutic decisions in lung cancer patients are in great part based on Eastern Cooperative
Oncology Group (ECOG) performance status. ECOG scale includes grades from 0 to 5, where grade
0 (patient is fully active, able to carry on all pre-disease performance without restriction), grade 1
(patient is restricted in strenuous activity but able to carry out a light work), and grade 2 (patient
is able of all selfcare, but unable to carry out any work activities and spends more than half of
a day outside the bed) allow considering the eligibility of the patient to chemotherapy [4]. Little is known, however, about the relation between dyspnea and ECOG performance status. Dyspnea is also important factor influencing
quality of life of the patients with lung cancer, and changes in quality
of life significantly influence the results of chemotherapy and survival
[5].
Thus the aim of the study was to evaluate the dyspnea in the elderly
patients with the advanced Non-Small Cell Lung Cancer (NSCLC)
and to answer the question to what extent subjectively and objectively
measured dyspnea influences the patients’ ECOG performance status
and whether dyspnea may be considered as a factor influencing the
results of palliative chemotherapy.
Table 1
Table 1
The comparison of age, TNM stage, coexistence of COPD and severe ischemic heart disease, nutritional status, number of received cycles of chemotherapy
and number of patients who completed the scheduled at least three cycles of chemotherapy in the patients with advanced NSCLC according to the ECOG 0 or ECOG
1 and ECOG 2 performance status.
Material and Methods
Material of the study consisted of 27 patients (19 men) aged over
65 years with advanced NSCLC, diagnosed and treated at the Lower
Silesian Center of Lung Diseases in Wroclaw, Poland, in the years
2015-16. Based on the TNM classification there were nine patients in
the stage IIIA, six patients in the stage IIIB and 12 patients in the stage
IV. The patients with clinical or radiological signs of brain metastases
were excluded from the study. There were nine patients who previously
underwent heart infarct and 12 patients were diagnosed with Chronic
Obstructive Pulmonary Disease (COPD). There were 17 patients who
had either COPD or underwent ischemic heart disease. There were 18
patients with ECOG 0, four patients with ECOG 1 and five patients
with ECOG 2 performance status. All the patients were scheduled for
the first-line palliative chemotherapy.
The patients underwent spirometric studies, fulfilled the Modified
Medical Research Council (mMRC) questionnaire, performed Six
Minutes Walk Test (6MWT) with Borg dyspnea scale, and fulfilled
COPD Assessment Test (CAT).
Spirometric study included the measurements of Forced Vital
Capacity (FVC), Forced Expiratory Volume in first second (FEV1)
and FEV1/FVC ratio calculation.
The mMRC was used to measure the grade of breathlessness on a
five-point scale, ranging from 0 to 4. Grade 0 indicates breathlessness
only with strenuous exercise, grade 1 – short of breath when hurrying
on level ground or walking up a slight hill, grade 2 – need to walking
slower than people of the same age on a level plane because of
breathlessness, grade 3 – need to stop for breath after walking about
100 meters or after a few minutes on level ground, and grade 4 –
breathlessness when dressing [6].
In the 6MWT the patients were asked to walk as far as possible
along a flat course during six minutes, instructed and encouraged
according to standard rules [7]. During 6MWT walking distance was
the primary outcome and the following measures were taken twice,
i.e. before and at the end of the test: oxygen saturation of hemoglobin
(SaO2) based on pulsoximetry recordings, heart rate and arterial
blood pressure measurements, and dyspnea score based on modified
Borg dyspnea scale.
The modified Borg scale allows to assess the dyspnea based on
10-items’ scale, describing the dyspnea as none, extremely mild, very
mild, mild, moderate, intense, rather intense, very intense, almost
unbearable or unbearable [8-10].
CAT is a questionnaire, containing the items regarding coughing
(from never to coughing all the time), feeling of having no phlegm
(mucus) in the chest or feeling that the chest is completely full of
phlegm, sensation that the chest does not feel tight at all to sensation
that the chest feels very tight, breathlessness or not while walking up
a hill or one flight of stairs, limitations doing activities at home (from
no limitations to being very limited), feeling confident/unconfident
leaving home despite/because of lung condition, sleeping soundly
or not sleeping soundly because of lung condition, having lots of
energy or having no energy at all [11]. In the eight-items CAT the
answers are scored from 0 to 5, thus the total score range is 0-40,
with the lowest values indicating better, and higher scores indicating
worse state of health [12]. As in the CAT questionnaire there are four
items that may be indirectly related to dyspnea (tightness in the chest,
limitations during activities at home, feeling unconfident leaving
home, lack of energy) and one item directly indicating dyspnea
(breathlessness while walking up a hill or upstairs) the scores in these
items were summed and analyzed separately. The score of these five
items derived from CAT was called modified CAT (mCAT). This
scale might vary from 0 to 25.
Informed consent has been obtained from all the patients
participating in the study.
A statistical software was used for all the measures (Statistica
for Windows, version 12). For descriptive data mean values with
Standard Deviation (SD) were used. In comparisons between the
groups non-parametric U Mann-Whitney test was used for data with
distributions of values different from normal and t-test for data with
normal distribution. A p value < 0.05 was considered significant.
Table 2
Table 2
The results of spirometric studies, mMRC dyspnea scale, 6MWT, and CAT score in the whole group of patients with advanced NSCLC and in the subgroups
with ECOG 0 and ECOG 1+ECOG 2 performance scale.
Results
Dyspnea, as evaluated in the subjective scales, such as mMRC,
Borg scale at rest, i.e. before 6MWT and in one item of CAT, was a
complaint of 21 patients (78%) before chemotherapy and only five
patients did not have dyspnea in any scale.
There were 16 patients who had dyspnea, as scored in the mMRC
scale: 13 patients – when hurrying on level ground or walking up a
slight hill (mMRC 1), two patients – enabling to walk as quickly as
people of the same age on a level plane (mMRC 2), two patients –
after walking about 100 meters or after a few minutes on level ground
(mMRC 3) and two patients – when dressing (mMRC 4).
There were nine patients who had dyspnea at rest, as scored in
the Borg scale before 6MWT: one patient described dyspnea as very
mild, four patients – as mild, three patients – as moderate, and one
patient – as rather intense.
There were 21 patients who had dyspnea while walking up a hill or
upstairs, as indicated in the item of CAT: four patients scored dyspnea as very mild (score 1- two patients) or mild (score 2- two patients),
two patients – as medium (score 3), 15 patients – as submaximal
(score 4- eight patients) or maximal (score 5- seven patients). The
scores in mCAT ranged from 0 to 19.
There was no correlation between mMRC and Borg scale at rest.
Score of mCAT positively correlated with the score in mMRC scale (r
= 0.68, p <0.05) and Borg scale at rest (r = 0.390, p <0.05).
Borg scale score increased significantly after 6MWT (Table 2),
both in the patients with ECOG 0 performance status (p <0.01) and in
the patients with ECOG 1 or ECOG 2 performance status (p <0.001).
The objective evaluation of dyspnea with 6MWT revealed the
distance ranging from 120 m to 430 m, mean 306.7 ± 93.8 m.
There was a negative correlation between the distance in the
6MWT with subjective score of dyspnea as evaluated in the Borg scale
at rest (r = -0.689, p <0.05) and with mCAT (r = -0.56, p <0.05), but
not with the total CAT score and not with the item of CAT directly
indicating dyspnea. There was no correlation between 6MWT distance and mMRC score.
Because both COPD and ischemic heart disease may cause
dyspnea the result were compared in the groups of 17 patients
with either COPD or heart infarct in anamnesis and in the group
of remaining 10 patients without any of these diseases. Dyspnea,
evaluated both subjectively (mMRC scale, Borg scale at rest, CAT
scores) or objectively (as 6MWT distance) was of similar intensity in
both groups.
In order to reveal possible relation between dyspnea and the
patients’ performance status, the groups of patients with ECOG 0
performance status were compared with the patients with ECOG 1
or ECOG 2 performance status (Table 1 and 2). The patients in both
groups were of similar age, with similarly advanced disease and with
similar frequency of concomitant diseases, such as COPD or heart
infarct in anamnesis. The patients in the ECOG 0 group had higher
BMI and more frequently were overweight or obese. The results of
spirometric studies were similar in both groups. In all the patients
there was a normal SaO2 at rest, similar in both groups and exceeding
94%.
In the subjective evaluation of dyspnea, the patients in the
ECOG1/ECOG2 group had higher scores in the mMRC and in some
items in CAT, i.e. in the item indicating dyspnea at one flight of stairs,
limitations doing activities at home, unconfident feeling leaving
home and lack of energy – leading to higher total score of CAT.
The sum of the item directly indicating dyspnea climbing the stairs
or walking up the hill and four items in CAT indirectly related to
dyspnea (i.e. mCAT) revealed higher score in the patients with ECOG 1 and ECOG 2 group. There were no differences in the subjective
evaluation of dyspnea in the Borg scale – both before or after 6MWT.
The objective measure of the distance in 6MWT revealed slightly, not
significantly, shorter distance in the patients in the ECOG 1/ECOG 2
group. Heart rate and arterial blood pressure in 6MWT did not differ
between the groups.
The comparison of the groups of patients who completed or
not-completed the scheduled at least three cycles of chemotherapy
revealed that non-completion of chemotherapy was associated with
smaller lung volumes and capacities (FEV1 and FVC) and more
severe dyspnea in objective measure of a distance in 6MWT, as well
in subjective measure in the Borg test before 6MWT (Table 3).
Table 3
Table 3
The comparison of the results of age, BMI, spirometric studies, CAT score mMRC dyspnea scale, and 6MWT in the patients with advanced NSCLC who
completed and non-completed the scheduled of at least three cycles of chemotherapy.
Discussion
In the elderly patients with advanced NSCLC dyspnea
differentiated the groups with ECOG 0 or ECOG 1/ECOG 2
performance status. The patients with ECOG 0 had lower mMRC
scores and lower scores of CAT.
mMRC is a scale of breathlessness recommended by the Global
Initiative for Chronic Obstructive Lung Disease (GOLD) to assess the
symptoms of the patients with COPD [13]. It can be also used in the
lung cancer patients [14,15].
In our elderly patients with advanced NSCLC the mean score was
slightly above 1 in the five-level mMRC scale (1.2 ± 1.2). In the COPD
patients mMRC score <2 is considered as a mark of slight symptoms
[13]. In our group of patients mMRC score was above 2 in the
patients with ECOG 1/ECOG 2 performance status and almost five times higher than in the patients with ECOG 0 performance status
(2.3 ± 1.2 vs. 0.5 ± 0.5, p <0.001). As mMRC allows to assess dyspnea
during daily activities, higher score of mMRC in the patients with
poorer performance status mirrored limited physical possibilities of
these patients.
The CAT was developed to measure dyspnea and other
components of quality of life in the COPD patients [11] and is also
recommended by GOLD to assess the symptoms of the COPD
patients [13]. The CAT serve not only to evaluate COPD patients
[12], but recently – also to evaluate the patients with interstitial lung
diseases [16]. To the best of our knowledge CAT was not used to
assess the symptoms of the patients with lung cancer.
In our elderly patients with NSCLC the mean CAT score was
15.3 ± 8.8 and was significantly higher in the patients with ECOG1
and ECOG 2 performance status that in the patients with ECOG 0
performance status (20.8 ± 8.7 vs. 12.6 ± 7.7, p <0.05). In the COPD
patients total CAT score of >10 indicates more severe symptoms [13].
Thus high score of CAT in our elderly patients with NSCLC, especially
in ECOG 1/ECOG2 group, indicated severely impaired health status.
In the eight-item CAT one question directly regards dyspnea,
i.e.– while climbing one flight of stairs or walking up the hill – and
in the scale from 0 to 5 our elderly patients with NSCLC reached the
mean value of 2.9 ± 2.0, that clearly indicated dyspnea on effort. The
dyspnea was much more severe in the patients with ECOG1/ECOG2
that in the ECOG 0 performance status patients (4.2 ± 1.3 vs. 2.3 ±
1.9).
After removing from CAT three items obviously not related to
dyspnea (describing cough, phlegm and sleep), the remaining five
questions were analyzed and called by the authors modified CAT,
i.e. mCAT. mCAT score was significantly (p <0.001), i.e. almost
2.5 times, higher in the patients with ECOG1/ECOG2 (13.0 ± 5.1)
than in the patients with ECOG 0 performance status (5.1 ± 5.1),
indicating more severe complaints related to dyspnea either directly
(the question about breathlessness while walking up a hill or upstairs)
or indirectly (the questions about tightness in the chest, limitations
during activities at home, feeling unconfident leaving home, and lack
of energy) in this group of patients.
The value of mCAT was confirmed by its positive correlation with
other subjective scales of dyspnea, such as mMRC and Borg scales,
and – especially – by its negative correlation with objective measure
of dyspnea, i.e. with the distance in the 6MWT. Thus our modification
of CAT, i.e. selection of five items directly or indirectly related to
dyspnea from CAT, allowed to find a tool clearly differentiating
ECOG 0 and ECOG1/ECOG 2 patients.
In contrast to mMRC and CAT, another subjective measure of
breathlessness, i.e. Borg scale, describes the sensation of dyspnea
at the moment of assessment. Borg scale might be used to evaluate
cancer patients [17]. In our elderly patients with advanced NSCLC,
evaluated at rest, the values of the Borg scale were very low (mean
0.9±1.4), with no differences related to ECOG performance status.
However, after an effort, i.e. after 6MWT, the scoring in the Borg scale
increased significantly in all the patients, and especially – almost three
times – in the patients with ECOG 1/ECOG 2 group (1.0 ± 1.2 to 2.8
± 2.2, p <0.001).
In contrast to subjective scales of dyspnea, there were no
differences in the objective measurement of distance in the 6MWT in
the patients with different ECOG performance status groups.
It should be also underlined that the objective measurements of
lung volumes were similar in the groups of patients with different
performance status, despite clear differences in subjectively perceived
dyspnea in mMRC scale and CAT. Similarly, the patients were not
hypoxemic, as indicated by normal SaO2 – both at rest and after
6MWT – and had similar SaO2 in ECOG 0 and in ECOG1/ECOG2
groups.
Interestingly, the nutritional status differentiated the groups with
ECOG 0 or ECOG 1/ECOG 2 patients. Most of the patients with
ECOG 0 performance status were overweight or obese, as compared
with only one obese patient with the ECOG 1 and no overweight or
obese patients with ECOG 2 performance status. Malnutrition is a
factor associated with low health-related quality of life in advanced
NSCLC [18].
The usefulness of the evaluation of dyspnea in the patients with
advanced NSCLC as a prognostic factor related to completion or notcompletion
of chemotherapy should be interpreted with caution and
regarded only as a preliminary data, as a group of our patients was
very small. However, it has been found that the objective measure
of dyspnea, i.e. markedly decreased distance in the 6MWT, and one
subjective measure, i.e. Borg scale at rest, were associated with noncompletion
of the scheduled chemotherapy. Although the patients
who not completed chemotherapy had also lower FEV1 and FVC ,
the measurements of dyspnea are also of importance, as spirometric
values may not correlate with 6MWT [19]. Small FEV1 was found
to be a strong predictor of mortality of the patients with advanced
NSCLC [20]. In our patients FEV1 in the patients who have not
completed chemotherapy was as low as 1.04 ± 0.1.
ECOG performance status remains one of the most important
factors related to prognosis in the patients with NSCLC receiving
chemotherapy [21,22]. This is especially important in the elderly
patients with advanced NSCLC [23]. Multiple co-morbidities and
decreased physiologic reserves of organ function, may result in higher
risk of toxicity of chemotherapy [24]. The problem of lung cancer in
elderly is important from epidemiological and clinical point of view
as about half of the patients is over 70 years old and the tendency of
incidence of lung cancer in the patients over 75 years is increasing
[25]. Both currently and in the past, however, underrepresentation
of elderly patients with lung cancer in clinical trials persists [26,27].
This may cause difficulties for physicians to make decisions regarding
starting chemotherapy in elderly. Thus comprehensive geriatric
assessment, encompassing several items in five domains, related
to medical problems, mental health, functional capacity, social
circumstances and environment [28] emerged in the assessment of
the elderly patients with lung cancer [29]. However, it appeared to be
not quite sufficient tool in the assessment of cancer patients because
of multiple problems related to its use and numerous alternative
instruments have been developed [30]. However, the problems of
dyspnea remains underrepresented in those instruments. Our study
added some information on the relations between both subjectively
perceived and objectively measured dyspnea and ECOG performance
status and the chances of completion of chemotherapy in elderly
patients with advanced NSCLC.
Conclusion
Dyspnea is a complaint of the majority of the elderly patients
with advanced NSCLC patients and is more severe in the patients with performance status higher than ECOG 0. 6MWT and modified
CAT are the best tools to evaluate dyspnea in the elderly patients with
advanced NSCLC starting palliative chemotherapy. The evaluation
of dyspnea may help to assess the performance status in the elderly
patients with advanced NSCLC.
Objective measurement of dyspnea, indicating shortened
distance in 6MWT may allow to predict unfavorable course of the
scheduled palliative chemotherapy in the elderly patients with
advanced NSCLC.
Acknowledgment
The work was financed from statutory activity (ST 831) of Medical University Wroclaw, Poland.
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