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Initial evaluation of the patient with lung cancer. Symptoms, sign, laboratory tests, and paraneoplastic syndromes

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Abstract

This chapter describes the components of the initial evaluation for a patient either suspected or known to have lung cancer. The components of the initial evaluation are based on the recognized manifestations of localized lung cancer, ie, symptoms referable to the primary tumor, intrathoracic spread of lung cancer, and patterns of metastatic dissemination. Features of the history and physical signs may be useful indicators of the extent of disease. A standardized evaluation, relying on symptoms, signs, and routinely available laboratory tests, can serve as a useful screen for metastatic disease. Also described are the common features of the various paraneoplastic syndromes associated with lung cancer.
DOI 10.1378/chest.07-1358
2007;132;149-160 Chest
Stephen G. Spiro, Michael K. Gould and Gene L. Colice
Guidelines (2nd Edition)
Evidenced-Based Clinical Practice
and Paraneoplastic Syndromes: ACCP Tests,Cancer: Symptoms, Signs, Laboratory
Initial Evaluation of the Patient With Lung
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Initial Evaluation of the Patient With
Lung Cancer: Symptoms, Signs,
Laboratory Tests, and Paraneoplastic
Syndromes*
ACCP Evidenced-Based Clinical Practice
Guidelines (2nd Edition)
Stephen G. Spiro, MD; Michael K. Gould, MD, FCCP; and
Gene L. Colice, MD, FCCP
Background: This chapter of the guidelines is intended to provide an evidence-based assessment
of the initial evaluation of patients recognized as having lung cancer and the recognition of
paraneoplastic syndromes.
Methods: The current medical literature that is applicable to this issue was identified by a
computerized search and was evaluated using standardized methods. Recommendations were
framed using the approach described by the Health and Science Policy Committee of the
American College of Chest Physicians.
Results: Patients with lung cancer usually present with multiple symptoms, both respiratory
related and constitutional. There is usually a time delay between symptom recognition by the
patient and the ultimate diagnosis of lung cancer by the physician. Whether this time delay
impacts prognosis is unclear, but delivering timely and efficient care is an important component
in its own right. Lung cancer may be accompanied by a variety of paraneoplastic syndromes.
These syndromes may not necessarily preclude treatment with a curative intent.
Conclusions: The initial evaluation of the patient with known or suspected lung cancer should
include an assessment of symptoms, signs, and laboratory test results in a standardized manner
as a screen for identifying those patients with paraneoplastic syndromes and a higher likelihood
of metastatic disease. (CHEST 2007; 132:149S–160S)
Key words: evaluation; laboratory tests; paraneoplastic syndrome; signs; symptoms
Abbreviations: ACTH adrenocorticotropic hormone; ADH antidiuretic hormone; HOA hypertrophic osteoar-
thropathy; LEMS Lambert-Eaton myasthenic syndrome; PTH parathyroid hormone; PTH-rP parathyroid hor-
mone-related peptide; SIADH syndrome of inappropriate antidiuretic hormone; SVCO superior vena cava
obstruction; VEGF vascular endothelial growth factor
L
ung cancer, unfortunately, is usually recognized
late in its natural history. In large part, this
reflects the peculiarities of pulmonary anatomy. A
pulmonary nodule could grow for a considerable
period of time, and potentially spread outside the
lung, before it would cause symptoms. Conse-
quently, at the initial presentation most patients with
lung cancer have advanced disease. In general, of
100 newly presenting patients with lung cancer, 80
will be inoperable at presentation and only approxi-
mately 20 will proceed to attempted resection.
1
These observations explain why the 5-year mortality
rates for lung cancer remain at approximately 85 to
90%. An understanding of how patients with lung
cancer initially present will possibly allow the earlier
identification of this increasingly common disease.
Materials and Methods
To update previous recommendations on the initial evaluation
of the patient with lung cancer, guidelines on lung cancer
diagnosis and management published between 2002 and May
Supplement
DIAGNOSIS AND MANAGEMENT OF LUNG CANCER: ACCP GUIDELINES
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2005 were identified by a systematic review of the literature (see
“Methodology for Lung Cancer Evidence Review and Guidelines
Development” section). Those guidelines including recommen-
dations that are specific to the initial evaluation of the lung cancer
patient were identified for possible inclusion in this section.
Supplemental material appropriate to this topic was obtained by
a literature search of a computerized database (MEDLINE).
Recommendations were developed by the writing committee,
graded by a standardized method (see “Methodology for Lung
Cancer Evidence Review and Guidelines Development” section),
and reviewed by all members of the lung cancer panel and the
Thoracic Oncology Network prior to approval by the Health and
Science Policy Committee, and the Board of Regents of the
American College of Chest Physicians.
Presenting Symptoms of Lung Cancer
Initial presenting symptoms in patients with lung
cancer may be respiratory related, but are often
constitutional and attributable to metastatic disease
(Table 1).
2–7
Cough is reported to be the most
common presenting symptom of lung cancer; other
respiratory symptoms include dyspnea, chest pain,
and hemoptysis.
8–10
Patients with lung cancer usu-
ally present with multiple symptoms, including both
respiratory and constitutional.
8,9
In a series of 678
consecutive lung cancer patients, at presentation 183
patients (27%) had symptoms related to the primary
tumor; 232 patients (34%) had nonspecific systemic
symptoms suggestive of metastases, including an-
orexia, weight loss and fatigue; and 219 patients
(32%) had symptoms specific to a metastatic site.
11
The percentage of patients found to have lung
cancer incidentally through chest radiographs has
been consistently low. In the series reported in 1970
by Carbone et al
11
of 678 consecutive newly diag-
nosed lung cancer patients in the United States, only
44 patients (6%) were asymptomatic. In a commu-
nity-based survey of lung cancer patients in Sweden
who had received new diagnoses between 1997 and
1999, only 24 of 364 patients (7%) were asymptom-
atic.
12
Buccheri and Ferrigno
8
described the initial
presentation of 1,277 consecutive lung cancer pa-
tients who received diagnoses at a single center in
Italy from 1989 to 2002. Only 154 of these patients
(13%) were asymptomatic at diagnosis. Prognosis in
lung cancer has been clearly related to the type of
presenting symptoms.
11
There was a better 5-year
survival rate reported for asymptomatic patients
(18%) than for those patients with symptoms related
to the primary tumor (12%). Those patients with
nonspecific symptoms had a 6% 5-year survival rate,
and those patients with symptoms indicating meta-
static disease fared the worst, with none alive at 5
years.
In addition to the time delay between the devel-
opment of the lung cancer and initial symptoms,
there are usually a series of other delays before
treatment is eventually initiated. Patients with lung
cancer may notice a new symptom or a change in
their usual respiratory symptoms but delay in report-
ing this to their general practitioner. Corner and
colleagues
9
interviewed 22 patients with newly diag-
nosed lung cancer in the United Kingdom. Patients
in this study had noted many different symptoms
prior to presentation to their general practitioner,
with cough and breathing changes being the most
common. Of note was that patients described the
onset of these symptoms between 4 months and 2
years (median time, 12 months) before they pre-
sented to their general practitioner. Koyi et al
13
reviewed the clinical course of 134 patients with lung
cancer in whom cancer was newly diagnosed in 1997
and 1998 in Graevleborg, Sweden. The mean delay
between symptom onset and first visit to their gen-
eral practitioner was 43 days (range, 0 to 256 days).
The one specific symptom that has been described as
prompting more rapid presentation was hemoptysis.
9
Even when patients present to the general practi-
tioner with a symptom compatible with lung cancer,
the general practitioner may not consider lung can-
cer a possibility. In the review by Koyi et al,
13
the
*From the Department of Respiratory Medicine (Dr. Spiro),
University College Hospital, London, UK; Veterans Affairs Palo
Alto Health Care System (Dr. Gould), Stanford, CA; and Pulmo-
nary, Critical Care, and Respiratory Services (Dr. Colice), Wash-
ington Hospital Center, Washington, DC.
The authors have reported to the ACCP that no significant
conflicts of interest exist with any companies/organizations whose
products or services may be discussed in this article.
Manuscript received May 30, 2007; revision accepted June 5,
2007.
Reproduction of this article is prohibited without written permission
from the American College of Chest Physicians (www.chestjournal.
org/misc/reprints.shtml).
Correspondence to: Stephen G. Spiro, MD, Department of Re-
spiratory Medicine, University College Hospital, Grafton Way,
London WC1E 6AU, UK; e-mail: stephen.spiro@uclh.nhs.uk
DOI: 10.1378/chest.07-1358
Table 1—Range of Frequencies of Initial Symptoms
and Signs of Lung Cancer*
Symptoms and Signs Range of Frequency, %
Cough 8–75
Weight loss 0–68
Dyspnea 3–60
Chest pain 20–49
Hemoptysis 6–35
Bone pain 6–25
Clubbing 0–20
Fever 0–20
Weakness 0–10
Superior vena cava obstruction 0–4
Dysphagia 0–2
Wheezing and stridor 0–2
*Modified from references 2 to 7.
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mean time from initial patient presentation to the
general practitioner and the general practitioner
obtaining a chest radiograph was 56 days (range, 0 to
477 days). This delay may be understandable. Al-
though lung cancer is a huge public health problem,
on average the general practitioner does not see lung
cancer patients often and usually has little personal
experience with the disease. It has been estimated
that a general practitioner in the United Kingdom
might encounter a new lung cancer patient only once
in every 8 months of regular practice.
14
In addition,
the presenting symptoms of lung cancer are nonspe-
cific, common, and more usually attributable to
benign causes. Okkes et al
15
reviewed detailed
records of patient encounters for 54 general practi-
tioners in the Netherlands from 1985 to 1995. For
patients who presented with cough (11,092 separate
patient encounters), lung cancer was not listed as a
separate entity among the 20 most common eventual
diagnoses. The 19th most common listing was “other
diseases of the respiratory tract.” This listing presum-
ably included lung cancer but only accounted for 3%
of all eventual explanations for cough as a presenting
symptom. Hamilton and colleagues
10
performed a
retrospective review of detailed general practitioner
records for 247 patients who presented with lung
cancer and compared the presenting symptoms in
these patients with matched control subjects taken
from the same general practitioners’ practices. They
found that the most common presenting symptoms
for lung cancer patients were poor predictors of the
eventual diagnosis. Even hemoptysis was more fre-
quently explained by benign conditions than by lung
cancer.
Delays in the eventual diagnosis of lung cancer
may also occur after referral of the patient to a
specialist consultant. In the study by Koyi et al,
13
on
average it took the consultant 33 days to establish the
diagnosis of lung cancer, but in 10% of all patients it
took 60 days to reach the diagnosis. This delay is
sometimes related to evaluating changes in either the
chest radiograph or chest CT scan over time, at least
in lung cancer patients who present with a solitary
nodule and in whom a wait-and-watch approach is
sometimes adopted (see the chapter in these guide-
lines on “Management of Patients With Pulmonary
Nodules”).
Overall, the time from recognition of the first
symptom related to lung cancer by the patient to
diagnosis of the disease and an eventual treatment
decision may be lengthy. For instance, in the careful
assessment of 134 patients in whom lung cancer had
been newly diagnosed in Sweden, on average it took
203 days from symptom onset to treatment deci-
sion.
13
How these delays might affect overall prog-
nosis for lung cancer, though, is not clear. In a small
study from California, a group of 84 patients who
underwent surgical resection of a stage I or II
non-small cell lung cancer was divided into those
who had an interval of 90 days between the initial
presentation and undergoing the actual operation
(n 46) and those with an interval of 90 days
(n 38).
16
The mean time from presentation to
operation for the entire group was 126 days (range, 1
to 641 days). No difference in 5-year survival was
found between those whose delay was 90 days and
those with a delay of 90 days. A larger study
17
of
1,082 patients with stage I and II lung cancer
reported from Spain found that delays between the
date of pathologic diagnosis and operation (mean
interval, 35 days; range, 1 to 154 days) did not affect
long-term survival. However, a study from Sweden
18
of 466 patients who had received treatment for
non-small cell lung cancer showed that patients with
more advanced disease had shorter time intervals
between the first symptoms and treatment (median
time delay from symptom to treatment for stage IV
disease: patients with advanced disease, 3.4 months;
patients with stage I-II disease, 5.5 months). Para-
doxically, patients with short treatment delays had a
worse prognosis, although the authors were unable
to fully control for the obvious selection biases that
confound observational studies of the relationship
between the timeliness of care and survival.
18
The relationship between the time from symptom
onset to lung cancer diagnosis and prognosis is not
clear. Confounding factors include tumor biology, as
well as issues relating to the health system and access
to care. Important considerations with delays in
treatment, besides potentially missing the opportu-
nity for cure or effective palliation, are the emotional
distress of patients and their family members. Al-
though further work is clearly needed to better
facilitate the process from identification of disease to
treatment decision for the lung cancer patient,
timely care for these patients should be expected.
The British Thoracic Society
19
recommended that all
patients with suspected lung cancer should be eval-
uated by a respiratory specialist within 7 days and
that the results of diagnostic tests should be commu-
nicated to the patient within 2 weeks. The RAND
Corporation, in a quality indicator published for lung
cancer care,
20
specified that a diagnosis of lung
cancer should be established within 2 months of
presentation and that treatment should begin within
6 weeks of diagnosis.
Recommendation
1. It is recommended that patients with
known or suspected lung cancer receive timely
and efficient care. Grade of recommendation, 1C
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Presenting Radiographic Features of Lung
Cancer
The chest radiograph plays a pivotal role in the
recognition of lung cancer. Certainly, in the asymp-
tomatic patient an abnormality on the chest radio-
graph would be the first clue to the presence of lung
cancer. In patients with symptoms related to the
primary tumor, the chest radiograph may often
strongly support a suspicion of carcinoma of the
lung. For patients presenting with either nonspecific
systemic complaints or symptoms suggestive of met-
astatic disease, the chest radiograph will be helpful in
focusing attention quickly on the lung as the most
likely primary site. The radiographic appearance of
lung cancer at initial presentation may be quite
variable. In general, lung cancers present slightly
more often on the right side than the left, and in the
upper lobes rather than in the lower lobes.
21–23
Lung
cancers may be seen centrally or peripherally, with a
predominance of central locations at presentation. It
has been estimated that up to 40% of the radio-
graphic findings associated with lung cancer are
related to central tumors causing airway obstruction
with secondary atelectasis and lung parenchyma
consolidation.
24,25
Peripheral tumors are classically
thought to present as solitary pulmonary nodules
(see chapter in these guidelines on “Management of
Patients With Pulmonary Nodules”), but could also
present radiographically as lung masses, ground-
glass opacities or complex abnormalities.
Clues from the chest radiograph may suggest the
diagnosis of lung cancer, but may not be helpful in
identifying a histologic subtype. Adenocarcinoma is
the most common type of lung cancer, accounting
for 30 to 35% of all cases.
26
Although adenocarcino-
mas are traditionally thought to occur more fre-
quently peripherally, they may develop centrally as
well. Squamous cell carcinoma may account for
about 30% of all lung cancers. They have typically
been thought to arise in the central bronchi and
extend into the hilum and mediastinum, but may also
develop in the lung parenchyma where they may
cavitate
27,28
; they may be slower growing and metas-
tasize late.
27
Large cell carcinoma comprises 10 to
20% of all lung cancers and is also seen more
commonly peripherally. Small cell lung carcinoma
comprises 15 to 25% of all lung cancers, and, like
squamous cell carcinoma, also usually develops in
the proximal airways and involves the hilum and
mediastinum. Unlike squamous cell carcinoma, evi-
dence of regional and/or distant metastatic disease at
the time patients present with small cell lung carci-
noma is the norm.
Symptoms Related to the Primary Tumor
Of the presenting symptoms in patients with lung
cancer, cough, dyspnea, chest pain, and hemoptysis
may be related to the primary tumor (Table 1).
Cough is the most common presenting symptom in
patients with lung cancer. Many lung cancers occur
in the central airways and may lead to postobstruc-
tive pneumonia or may cause lymph node enlarge-
ment, which may lead to cough. The failure of acute
exacerbations of COPD to clear should raise suspi-
cion of the presence of a neoplasm. Dyspnea devel-
ops commonly and is usually associated with increas-
ing cough and amounts of sputum. If the tumor is
occluding a main airway, it can cause breathlessness,
which may be associated with a unilateral wheeze.
Chest discomfort is also commonly reported by lung
cancer patients at diagnosis. This is often of an
ill-defined nature, intermittent and aching in quality.
Definite pleuritic pain may occur as a result direct
spread of the tumor to the pleural surface.
Hemoptysis is a common presenting symptom in
patients with lung cancer. It is rarely severe and
usually consists only of blood streaking of the spu-
tum. The most common description is that of cough-
ing up blood for several days in succession. The chest
radiograph finding is usually abnormal in patients
with hemoptysis from lung cancer. However, it has
been estimated that up to 5% of patients with
hemoptysis and either a normal chest radiograph
finding or a chest radiograph finding with no local-
izing abnormalities will have lung cancer.
29
Lung
cancers in these cases may be within the endobron-
chial tree, an area in which even CT scanning may
fail to detect the cancer.
30
Consequently, in patients
presenting with hemoptysis who are 40 years of
age and have COPD and a history of smoking, even
though the chest radiograph findings may be unre-
markable, there should still be a high index of
suspicion for lung cancer. Besides careful observa-
tion, the clinician may consider further diagnostic
tests, such as chest CT scan or bronchoscopy. Spu-
tum cytology may be a useful screening tool in these
patients.
29
Symptoms and Signs of Intrathoracic
Spread
The intrathoracic spread of lung cancer, either by
direct extension or lymphatic spread, produces a
variety of symptoms and signs. These may be caused
by the involvement of nerves (eg, recurrent laryngeal
nerve, phrenic nerve, brachial plexus, and sympa-
thetic nerve trunks), chest wall and pleura, vascular
structures (eg, superior vena cava, pericardium, and
heart), and visceral structures (eg, the esophagus).
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Recurrent laryngeal nerve palsy, which causes
hoarseness, has been reported in 2 to 18% of lung
cancer patients. It is more common in left-sided
tumors because of the circuitous route of the left
recurrent laryngeal nerve around the aortic arch. It is
associated with poor expectoration with coughing
and an increased risk of aspiration. Phrenic nerve
dysfunction may be noted on the chest radiograph by
the presence of an elevated hemidiaphragm, or it can
present with breathlessness in patients already com-
promised by lung disease. The superior sulcus or
Pancoast tumor arises posteriorly in the apex of an
upper lobe near the brachial plexus, commonly
infiltrating the eighth cervical nerve root and the first
and second thoracic nerve roots. This causes pain,
cutaneous temperature change, and muscle wasting
along the relevant nerve root. Symptoms and signs
may be misleading initially, often resulting in a delay
of many months before the true diagnosis is re-
vealed. Horner syndrome occurs because of the
involvement of the sympathetic chain and stellate
ganglion, and is recognized by the typical triad of
small pupil with ipsilateral ptosis and lack of facial
sweating.
Chest wall and pleural invasion by the primary
tumor, causing localized chest pain, is a common
presenting symptom. More than 50% of patients
with lung cancer complain of chest pain during the
course of their disease. The pain is usually dull, tends
to be persistent, poorly localized, and unrelated to
breathing or coughing. Retrosternal pain may be due
to hilar and mediastinal nodal involvement. When
chest pain is particularly severe, persistent, and
localized, it is usually related to either direct invasion
of the pleura or chest wall by the primary tumor, or
to a rib metastasis. Tenderness may be elicited at the
site of rib involvement, and, rarely, a soft tissue mass
can be palpated. Pleural involvement occurs in 8 to
15% of patients with lung cancer. Pleuritic chest pain
can occur with the early phase of neoplastic pleural
invasion but may disappear with the onset of a
pleural effusion. Pleural effusion, which may result
in dyspnea, is generally caused by direct pleural
extension but may also be secondary to mediastinal
node involvement and lymphatic obstruction.
Lung cancer accounts for 46 to 75% of all cases of
superior vena cava obstruction (SVCO). The most
common histologic subtype associated with SVCO is
small cell carcinoma.
4,31,32
Direct invasion by the
primary tumor into the mediastinum or lymphatic
spread with enlarged right paratracheal metastatic
lymph nodes causes the SVCO. The patient will
complain of swelling of the face, including the neck
and eyelids, upper torso, neck, and arms. Dilated
veins will be visible over the upper torso, shoulders
and arms. Other symptoms related to SVCO include
headache, dizziness (particularly on bending for-
wards), drowsiness, blurring of vision, cough, and
dysphagia.
31,33
Metastases to other vascular struc-
tures in the mediastinum, such as the heart and
pericardium, usually occur by direct lymphatic
spread. At autopsy, cardiac involvement occurs in
about 15% of patients, and a small number of
patients will have tamponade.
34
In patients with
primary lung cancer, the pericardium is the most
common site of cardiac involvement, causing an
effusion or supraventricular arrhythmias.
35
Metastatic disease causing enlargement of the
subcarinal lymph nodes can cause dysphagia by
compressing the middle third of the esophagus. Very
occasionally, tracheal primary tumors may grow into
the esophagus, also causing dysphagia.
Symptoms, Signs, and Laboratory Tests
Indicating Extrathoracic Metastases
About one third of patients present with symptoms
as a result of distant metastases. The most common
sites of distant metastasis from lung cancer are the
bones; liver; adrenal glands and intraabdominal
lymph nodes; brain and spinal cord; and lymph
nodes and skin. Lung cancer can metastasize to
virtually any bone, although the axial skeleton and
proximal long bones are most commonly involved.
The primary symptom resulting from bone involve-
ment is pain, which may have a pleuritic component
when the ribs are involved. Bone pain is present in
up to 25% of all patients at presentation.
Liver metastases occur commonly with lung can-
cer. However, liver function test results are seldom
abnormal until the metastases are numerous and
large, or they block the hepatic ducts, which is when
jaundice will occur. Hepatic metastases most com-
monly produce symptoms of weakness and weight
loss. When present, hepatic metastases carry a very
poor prognosis. Adrenal lesions and paraaortic lymph
node metastases may occur and are most commonly
seen with small-cell lung cancers; in the latter cell
type, they are often discovered during staging. Clin-
ical evidence of adrenal insufficiency is rarely seen.
Intracranial metastases occur in 10% of lung can-
cer patients at presentation. Spinal cord metastases
are less common and tend to occur in patients with
cerebral metastases. Brain metastasis may produce
headache, nausea and vomiting, focal neurologic
symptoms or signs, seizures, confusion, and person-
ality changes. The lung is the primary site of approx-
imately 70% of cancers that initially present with
symptomatic brain metastases.
36
The most common site of palpable lymphadenop-
athy is the supraclavicular fossa, which can be in-
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volved in 15 to 20% of cases during the course of the
disease. Identifying an enlarged lymph node or
subcutaneous nodule due to metastatic lung cancer
is extremely helpful in facilitating both diagnosis and
staging. Fine-needle aspiration can be performed
quickly at the bedside or as an outpatient with little
morbidity and with a high sensitivity.
37
Standardized Evaluation for Systemic Metastases
Carbone et al
11
and Feinstein and colleagues
38–42
have explored the relationship between symptoms at
presentation and prognosis in a large cohort of
consecutive lung cancer patients. Patients with the
best prognosis were either asymptomatic or had
symptoms referable only to the primary tumor. In
patients either with systemic symptoms of anorexia,
weight loss, and fatigue or with symptoms attribut-
able to metastatic disease, prognosis was especially
poor. The relationship between systemic symptoms
and prognosis was conserved with standard staging of
lung cancer. Within any individual tumor stage,
there was a gradient of worsening prognosis in
patients who presented with anorexia, weight loss,
and fatigue. The biological association between sys-
temic symptoms and worse prognosis was not en-
tirely clear, although, intuitively, patients with sys-
temic symptoms would be clinically suspected of
having extensive disease.
Hooper and colleagues
43,44
used a cluster of clin-
ical factors, including symptoms, signs, and standard
laboratory tests, to screen patients for metastatic
disease. Included within these clinical factors were
weight loss and anemia. They found that abnormal-
ities in these factors were associated with radio-
graphic evidence of metastatic disease. The more
abnormalities noted in the clinical assessment, the
more likely that metastases would be detected. They
also found that patients with no abnormalities in
these clinical factors were extremely unlikely to have
evidence of metastatic disease found on a CT scan.
Silvestri et al
45
adapted the criteria of Hooper et
al
43,44
(Table 2) and retrospectively asked whether
they would be a useful screen for detecting adrenal
metastases. As with the work by Hooper et al,
43,44
if
no clinical abnormalities were noted, adrenal metas-
tases were not found by CT scan; the more clinical
abnormalities that were found, the more likely it was
that adrenal metastases would be found. Both the
work by Silvestri et al
45
and a study by Quinn and
coworkers
46
pointed out that abnormalities in the
clinical assessment would often not be helpful in
identifying the site of metastases. However, the
recognition of abnormalities in the clinical screen
strongly suggested the presence of metastases.
Silvestri et al
45
also considered whether clinical
evaluation would be useful in identifying which
patients with lung cancer would have extrathoracic
metastases detected by CT scanning of the brain or
abdomen or by radionuclide bone scans.
47
They
performed a metaanalysis
47
of all studies in lung
cancer patients that provided data on both radio-
graphic studies and the clinical factors adapted from
the criteria of Hooper et al.
43,44
Consistent with
earlier work, this metaanalysis showed that patients
with clinical abnormalities were often found to have
metastatic disease. However, if no abnormalities
were noted in the clinical assessment, patients were
very unlikely to have evidence of metastatic disease
on CT scans of the brain or abdomen or on radio-
nuclide bone scans. These authors concluded that
performing an assessment of various clinical factors
through a thorough history and physical examination,
and standard laboratory tests would be a useful
screen for identifying patients with a higher likeli-
hood of metastatic disease.
Recommendation
2. It is recommended that all patients with
known or suspected lung cancer give a thor-
ough history and undergo a thorough physical
examination and standard laboratory tests as a
screen for metastatic disease. Grade of recom-
mendation, 1B
Paraneoplastic Syndromes
Paraneoplastic syndromes are a group of clinical
disorders that are associated with malignant diseases
Table 2—Features of a Standardized Evaluation for Systemic Metastases*
Symptoms Signs Laboratory Tests
Constitutional: weight loss 10 lb Lymphadenopathy (1 cm) Hematocrit 40% in men
Musculoskeletal: focal skeletal pain Hoarseness, superior vena cava syndrome Hematocrit 35% in women
Neurologic: headaches, syncope, seizures,
extremity weakness, or recent change in
mental status
Bone tenderness, hepatomegaly (13-cm
span), focal neurologic signs, papilledema,
and soft tissue mass
Elevated alkaline phosphatase, -
glutamyltransferase, or serum
glutamicoxaloacetic transaminase level
*Modified from references 42 and 44.
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that are not directly related to the physical effects of
primary or metastatic tumors.
48,49
Paraneoplastic
syndromes may occur in 10% of patients with bron-
chogenic carcinoma.
2,3
The extent of paraneoplastic
symptoms is unrelated to the size of the primary
tumor, and in some cases can precede the diagnosis
of malignant disease. At other times they may occur
late in the illness, or herald the first sign of recur-
rence. The exact mechanism by which paraneoplastic
syndromes occur is not fully understood in all cases,
but in many cases it appears to be related to either
the production of biologically active substances by
the tumor itself (eg, polypeptide hormones or cyto-
kines) or in response to the tumor (eg, antibodies).
Although a wide variety of paraneoplastic syndromes
have been associated with lung cancer (Table 3), the
most commonly recognized include endocrine, joint,
and neurologic abnormalities.
Common Endocrine Paraneoplastic Syndromes
Associated With Lung Cancer
Hypercalcemia: The incidence of hypercalcemia
in patients with lung cancer ranges from 2 to 6% at
presentation to 8 to 12% throughout the course of
the disease. Symptoms include nausea, vomiting,
abdominal pain, constipation, polyuria, thirst, dehy-
dration, confusion, and irritability. Squamous cell
carcinoma is most frequently associated with hyper-
calcemia. Although bone metastases may be found in
patients with lung cancer and hypercalcemia, most
commonly humoral mechanisms account for the
hypercalcemia.
50,51
Bioassays have suggested that
there are increased levels of parathyroid hormone
(PTH)-like activity in lung cancer patients with
hypercalcemia.
52
Increased levels of urinary cyclic
adenosine monophosphate have been reported in
lung cancer patients, which is consistent with an
increased PTH effect.
53
However, serum immuno-
reactive PTH levels are low to undetectable in
patients with lung cancer and hypercalcemia.
54
A
protein with PTH-like activity has been purified
from lung cancer cell lines.
55,56
Increased bone
resorption as the explanation for hypercalcemia has
been attributed to this PTH-related protein (PTH-
rP) released from lung cancer cells.
50
Serum levels of
PTH-rP may be a valuable indicator of survival in
lung cancer patients. Hiraki et al
57
found in a small
group of patients with lung cancer and hypercalce-
mia that elevated circulating levels of PTH-rP were
associated with shorter survival times. Increased
serum PTH-rP levels were also associated with a
higher likelihood of bony metastases. The authors
speculated that PTH-rP, besides increasing bone
resorption, might also play a role in facilitating bone
metastases.
Syndrome of Inappropriate Antidiuretic Hormone
Production: Hyponatremia, the most obvious sign of
syndrome of inappropriate antidiuretic hormone
Table 3—Paraneoplastic Syndromes Associated With
Lung Cancer*
Endocrine syndromes
SIADH production
Nonmetastatic hypercalcemia
Cushing syndrome
Gynecomastia
Hypercalcitonemia
Elevated levels of LSH and FSH
Hypoglycemia
Hyperthyroidism
Carcinoid syndrome
Neurologic syndromes
Subacute sensory neuropathy
Mononeuritis multiplex
Intestinal pseudo-obstruction
LEMS
Encephalomyelitis
Necrotizing myelopathy
Cancer associated retinopathy
Skeletal syndromes
Hypertrophic osteoarthropathy
Clubbing
Renal syndromes
Glomerulonephritis
Nephrotic syndrome
Metabolic syndromes
Lactic acidosis
Hypouricemia
Systemic syndromes
Anorexia and cachexia
Fever
Collagen-vascular syndromes
Dermatomyositis
Polymyositis
Vasculitis
Systemic lupus erythematosus
Cutaneous
Acquired hypertrichosis languinosa
Erythema gyratum repens
Erythema multiforme
Tylosis
Erythroderma
Exfoliative dermatitis
Acanthosis nigricans
Sweet syndrome
Pruritus and urticaria
Hematologic
Anemia
Leucocytosis and eosinophilia
Leukemoid reactions
Thrombocytosis
Thrombocytopenic purpura
Coagulopathies
Thrombophlebitis
Disseminated intravascular coagulation
*LSH lutein-stimulating hormone; FSH follicle-stimulating
hormone. Modified from references 1 and 11.
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(SIADH) production, has been reported to occur in
a wide incidence of lung cancer patients. Elevated
antidiuretic hormone (ADH) levels and impaired
water handling are found in possibly 30 to 70% of
patients with lung cancer,
50
but the production of
excess ADH does not always produce symp-
toms.
58–60
Only 1 to 5% of lung cancer patients have
symptoms that are attributable to the SIADH pro-
duction. Manifestations of SIADH production in-
clude confusion, unexplained seizures, decreased
level of consciousness, and coma. Biochemically, the
SIADH production is defined as low serum sodium
and a dilute plasma osmolality along with a higher, or
“inappropriate,” urine osmolality, in the presence of
continued urinary sodium excretion. The SIADH
production is mainly associated with small cell lung
cancer, although other malignant tumors of the lung
may rarely be associated with this syndrome.
58,61,62
Although a variety of hormones, including atrial
natriuretic peptide, have been implicated as possibly
contributing to the hyponatremia found in lung
cancer patients, hormone assays performed under
controlled settings have shown that elevated plasma
ADH levels are consistently found in these patients
and seem to explain the impaired ability to excrete a
water load.
63
The excess levels of ADH have been
reported to originate from either ectopic production
by lung cancer cells
59
or inappropriate peripheral
baroreceptor stimulation of ADH release from the
hypothalamus.
63
The syndrome resolves promptly
(within 3 weeks) with the initiation of combination
cytotoxic chemotherapy in 80% of patients with small
cell lung cancer, but commonly recurs with tumor
progression.
64
Cushing Syndrome: Ectopic production of adre-
nocorticotropic hormone (ACTH) by small cell lung
cancer cells is the most common explanation for
Cushing syndrome.
50
ACTH is the most commonly
produced ectopic hormone in lung cancer patients.
It is not unusual to find increased serum levels of
ACTH in patients with lung cancer; it may be
detectable in up to 50% of patients with lung
cancer.
65
However, some patients with Cushing syn-
drome may have normal basal ACTH levels.
66
In
these patients, precursors of ACTH, such as proopio-
melanocortin, may be elevated, suggesting that
Cushing syndrome could develop due either to
ectopic production or to aberrant processing of
ACTH by small cell lung cancer cells.
50
Clinical
manifestations of Cushing syndrome, which include
weakness, muscle wasting, drowsiness, confusion,
possible psychosis, dependent edema, moon facies,
hypokalemic alkalosis, and hyperglycemia, are found
in only a very small proportion of lung cancer
patients. Cushing syndrome has been described in 1
to 5% of patients with small cell carcinoma,
67,68
but
this may be an overestimate. In a 2005 report
66
of the
National Institutes of Health experience with Cush-
ing syndrome, only 3 of the 90 cases were attributed
to small cell lung cancer. Most commonly, Cushing
syndrome occurred in patients with pulmonary car-
cinoid (35 of 90 patients). Resection of the primary
tumor, if possible, will effectively treat Cushing
syndrome. Most patients with Cushing syndrome
due to small cell lung cancer present with extensive
stage disease and have a poor response to chemo-
therapy.
50
Digital Clubbing and Hypertrophic
Osteoarthropathy
Digital clubbing is an enlargement of the terminal
segments of the fingers and/or toes due to prolifer-
ation of connective tissue beneath the nail matrix.
Quantitative indexes of the nail profile angle, hy-
ponychial angle and phalangeal depth ratio can be
determined to assist in identifying clubbing.
69
Hy-
pertrophic osteoarthropathy (HOA) is a systemic
disorder, which involves both a painful symmetrical
arthropathy, usually of the ankles, wrists, and knees,
and periosteal new bone formation in the distal long
bones of the limbs. Histologic features of HOA
include vascular hyperplasia, edema, and excessive
fibroblast and osteoblast proliferation.
70
Clubbing and HOA may be associated with any
cell type of lung cancer, although they are associated
most frequently with squamous cell carcinoma and
adenocarcinoma, and least frequently with small cell
lung carcinoma. The exact mechanism responsible
for the development of clubbing and HOA is un-
known. In the past, explanations included neuro-
genic, hormonal, and vascular mechanisms.
71
More
recently, the overexpression of vascular endothelial
growth factor (VEGF) has been implicated as con-
tributing to the pathogenesis of clubbing and HOA.
In the case of a young woman with lung cancer and
HOA, serum VEGF levels were initially elevated;
after resection of the cancer, the serum VEGF levels
fell and HOA remitted. Histochemical studies of the
resected tumor showed increased VEGF messenger
RNA expression, suggesting ectopic production by
the lung cancer cells.
70
Clubbing is much more common than HOA. In
one study
72
of 111 consecutive patients with patho-
logically proven lung cancer, clubbing was present in
32 patients (29%). The phenomenon was signifi-
cantly more common among women than men (40%
vs 19%, respectively), and in patients with non-small
cell lung cancer than in those with small cell lung
cancer (35% vs 4%, respectively).
72
HOA is seen in
5% of patients with non-small cell lung cancer.
73
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Small cell lung cancer is a rarer cause of HOA; in one
series,
74
it accounted for only 1% of the patients with
HOA. Anecdotal observations indicate that clubbing
and HOA may resolve with successful treatment of
the primary tumor, particularly surgical resection of
a non-small cell lung cancer.
Neurologic Syndromes
A variety of poorly understood neurologic syn-
dromes may occur in patients with lung cancer.
46
The diagnosis of a neurologic paraneoplastic syn-
drome is made once other causes, such as electrolyte
imbalance, metastatic disease, cerebral and spinal
vascular disease, infections, and treatment toxicity,
are excluded. The neurologic syndromes include the
Lambert-Eaton myasthenic syndrome (LEMS), lim-
bic encephalopathy, polyneuropathy, cerebellar de-
generation, retinopathy, opsoclonus-myoclonus, and
autonomic neuropathy.
75,76
In LEMS, which is the
most widely recognized of these disorders, patients
present with the gradual onset of proximal lower
extremity weakness; proximal upper extremity weak-
ness is usually less noticeable. The syndrome may be
worse in the morning and improve during the day.
Although extraocular muscle involvement is uncom-
mon, ptosis is often found.
77
Paraneoplastic neuro-
logic syndromes have been associated almost exclu-
sively with small cell lung cancer. These syndromes
have been reported to affect 4 to 5% of lung cancer
patients,
75
but the incidence is probably lower. In
1991, Elrington et al
78
reported that in a prospective
survey of 150 consecutive cases of small cell lung
cancer only two patients (1%) had LEMS and one
patient (1%) had a polyneuropathy. A 2005
study
76
of 432 consecutive patients with small cell
lung cancer showed similar results. LEMS was found
in seven patients (1.6%), polyneuropathy in two
patients (1%), subacute cerebellar degeneration in
one patient (1%), and limbic encephalitis in three
patients (1%).
76
The severity of the neurologic
symptoms is unrelated to tumor bulk; in fact, the
syndromes seem to be found more often in patients
with limited disease, and in some patients a primary
malignant lesion may be undetected before death
despite disabling symptoms.
76,78–80
The neurologic syndromes associated with lung
cancer seem to develop through autoimmune mech-
anisms. Nearly all of the paraneoplastic neurologic
syndromes are associated with the presence of type 1
antineuronal nuclear antibodies (also known as
anti-Hu antibodies).
81
The Hu antigen is normally
found in neurons, but, because the developing CNS
is sequestered from the immune system by the
blood-brain barrier, healthy adults do not have
anti-Hu antibodies. Small cell lung cancers express
Hu antigen, and up to 20% of patients with small cell
lung cancer have detectable circulating levels of
anti-Hu antibodies, although paraneoplastic neuro-
logic syndromes will not develop in all of these
patients.
76,82
In patients with LEMS, IgG antibodies
directed against the P/Q voltage-gated presynaptic
calcium channel interfere with Ca⫹⫹-dependent
neurotransmitter release.
83,84
At autopsy, lympho-
cytic inflammatory infiltrates in patients with para-
neoplastic neurologic syndromes are found in areas
of the nervous system that correspond to the neuro-
logic deficits, supporting the concept that the auto-
antibodies play a key role in the pathogenesis of the
neurologic syndromes. Lymphocytic infiltrates have
also been found around the primary tumor, suggest-
ing that the immune response may actually limit
progression of the underlying small cell lung
cancer.
85
The response of the neurologic paraneoplastic
syndrome to effective chemotherapy in patients with
small cell lung cancer is variable.
86,87
Sustained
improvements in the neurologic symptoms have
been reported, although this is less commonly seen
in patients with motor or sensory neuropathies.
88
In
a small series
89
of patients with small cell lung
cancer, the overall prognosis was more favorable in
those patients with LEMS than in those without it.
Recommendation
3. It is recommended that patients with lung
cancer and a paraneoplastic syndrome not be
precluded from potentially curative therapy on
the basis of these symptoms alone. Grade of
recommendation, 2C
Summary
Most patients with lung cancer will be symptom-
atic at presentation. A minority of patients presents
with symptoms related to the primary tumor, but
most patients present with either nonspecific sys-
temic symptoms, including anorexia, weight loss, and
fatigue, or specific symptoms indicating metastatic
disease. Asymptomatic patients and patients with
symptoms related to the primary tumor have better
5-year survival rates than those patients with sys-
temic symptoms or symptoms indicating metastatic
disease. The initial evaluation of the patient with
known or suspected lung cancer should include an
assessment of symptoms, signs, and laboratory test
results in a standardized manner as a screen for
identifying those patients with a higher likelihood of
metastatic disease.
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Paraneoplastic syndromes, which occur in up to
10% of patients with lung cancer, are a group of
clinical disorders that are associated with malignant
diseases not directly related to the physical effects of
primary or metastatic tumors. These syndromes may
be due to the production of biologically active
substances, such as polypeptide hormones, antibod-
ies, or cytokines. Paraneoplastic symptoms are unre-
lated to the size of the primary tumor, in some cases
can precede the diagnosis of malignant disease, and
at other times may occur late in the illness or may
herald the first sign of recurrence.
Summary of Recommendations
1. It is recommended that patients with
known or suspected lung cancer receive
timely and efficient care. Grade of recom-
mendation, 1B
2. It is recommended that all patients
with known or suspected lung cancer give a
thorough history, and undergo a thorough
physical examination and standard labora-
tory tests as a screen for metastatic disease.
Grade of recommendation, 1C
3. It is recommended that patients with
lung cancer and a paraneoplastic syndrome
not be precluded from potentially curative
therapy on the basis of these symptoms
alone. Grade of recommendation, 2C
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... several common signs and symptoms associated with lung cancer, which can be classified as a result of the primary tumour, etastases, paraneoplastic syndromes or they may be non-specific symptoms. 3 The most common signs and symptoms relating to a primary lung tumour, and therefore corresponding to early stage disease, are: cough, dyspnea discomfort) haemoptysis (coughing up blood) and chest discomfort. Non-specific symptoms loss or fatigue are also common in the initial stages of lung cancer. ...
... Non-specific symptoms loss or fatigue are also common in the initial stages of lung cancer. 3 Pain and dyspnea have been reported to be common distressing symptoms in people with cancer. Beckles et al (2003) report 25% of people with lung cancer will experience bone pain and 20 to 49% will experience chest pain, somewhere While the incidence of dyspnea in people with lung cancer has been reported to be at least as frequent as pain, its presence is underappreciated and potentially not scrutinized or investigated to the same of the database Scopus reveals almost twice as much literature addressing pain and While the prevalence of shortness of breath has been reported to be as frequent as pain in people with lung cancer, less review of the literature was undertaken to investigate how this symptom has been assessed and whether breathlessness in people with lung cancer is identified and included in this review. ...
... 3 Pain and dyspnea have been reported to be common distressing symptoms in people with cancer. Beckles et al (2003) report 25% of people with lung cancer will experience bone pain and 20 to 49% will experience chest pain, somewhere While the incidence of dyspnea in people with lung cancer has been reported to be at least as frequent as pain, its presence is underappreciated and potentially not scrutinized or investigated to the same of the database Scopus reveals almost twice as much literature addressing pain and While the prevalence of shortness of breath has been reported to be as frequent as pain in people with lung cancer, less review of the literature was undertaken to investigate how this symptom has been assessed and whether breathlessness in people with lung cancer is identified and included in this review. A variety of outcome measures have been used to assess the experience of dyspnea with domains including essness appears to be variable, with some studies reporting it to be the most distressing sensation, while others report lower levels of distress. ...
Article
While the prevalence of shortness of breath has been reported to be as frequent as pain in people with lung cancer, less attention has been paid to the distress associated with this symptom (dyspnea). This systematic review of the literature was undertaken to investigate how this symptom has been assessed and whether breathlessness in people with lung cancer is distressing. Using a pre-determined search strategy and inclusion criteria, thirty-one primary studies were identified and included in this review. A variety of outcome measures have been used to assess the experience of dyspnea with domains including intensity, distress, quality of life, qualitative sensation and prevalence. The distress associated with breathlessness appears to be variable, with some studies reporting it to be the most distressing sensation, while others report lower levels of distress. Overall the studies reflect a high prevalence of dyspnea in lung cancer patients, with subjects experiencing a moderate level of dyspnea intensity and interference with activities of daily living. Overall, the findings of this review indicate that dyspnea was a common symptom experienced by people with lung cancer with varying degrees of intensity and unpleasantness. Thus, if dyspnea and pain are both distressing sensations for people with lung cancer, this has potential implications for both clinical and academic areas, with regards to both management strategies and further research.
... The study shows that the symptoms of lung cancer vary based on the cancer stage. When the cancer cell appears on the lung, the physiological symptoms are not prominent, wherein most of the cases, the patients and the observant do not find any difference [14]. However, as the cancerous cells start spreading, the symptoms start becoming apparent. ...
... Then morphological opening with ellipsoid has 90-pixel major axis and 10-pixel height. It is applied on both masks followed by another complement operation defined by (14). Here, M o stands for morphological opening, and the X mask represents both left and right masks. ...
Article
Lung cancer, also known as pulmonary cancer, is one of the deadliest cancers, but yet curable if detected at the early stage. At present, the ambiguous features of the lung cancer nodule make the computer-aided automatic diagnosis a challenging task. To alleviate this, we present LungNet, a novel hybrid deep-convolutional neural network-based model, trained with CT scan and wearable sensor-based medical IoT (MIoT) data. LungNet consists of a unique 22-layers Convolutional Neural Network (CNN), which combines latent features that are learned from CT scan images and MIoT data to enhance the diagnostic accuracy of the system. Operated from a centralized server, the network has been trained with a balanced dataset having 525,000 images that can classify lung cancer into five classes with high accuracy (96.81%) and low false positive rate (3.35%), outperforming similar CNN-based classifiers. Moreover, it classifies the stage-1 and stage-2 lung cancers into 1A, 1B, 2A and 2B sub-classes with 91.6% accuracy and false positive rate of 7.25%. High predictive capability accompanied with sub-stage classification renders LungNet as a promising prospect in developing CNN-based automatic lung cancer diagnosis systems.
... It turns out that amino acid position 3 was the single most important position for deciding receptor affinity towards GRP, but that a particular arrangement of the amino acid sequence Cys- screening guidelines are seldomly adhered to either due to limited access to primary care or patient unwillingness to undergo screening if they are asymptomatic. In fact, the insidious onset of the clinical signs and symptoms of lung cancer are a known culprit for delayed diagnosis and treatment of SCLC and lung cancers in general [14]. The most common presenting signs and symptoms of SCLC are cough, dyspnea, hemoptysis, and chest pain [15], all of which are non-specific and often overlap with symptoms of other comorbid conditions such as chronic obstructive pulmonary disease. ...
Article
Small cell lung cancer (SCLC) is a aggressive form of primary lung neoplasm that often presents in elderly smokers. While stage I SCLC can be managed with surgery, extensive-stage disease is managed with chemotherapy using etoposide and cisplatin among other agents, and often complemented by radiation therapy to the chest and cranium. Recent advances in pharmacological research have yielded novel antibody and peptide-conjugated adjunctive chemotherapy, of which bombesin and bombesin receptors have played an important role due to their overexpression in SCLC and other lung cancers. Chemotherapy agents conjugated to bombesin or bombesin-like peptides often demonstrate higher therapeutic efficacy, greater treatment specificity, as well as improved cytotoxicity towards SCLC cells that demonstrate drug resistance. Further modifications to the bombesin-drug conjugate, such as liposomal preparation, have further enhanced bio-availability and half-life of the compound. Additionally, bombesin-radioisotope conjugates can be used for early detection of SCLC using positron emission tomography, as well as subsequent targeted adjuvant radiotherapy to help minimize radiation-induced fibrosis of healthy tissue. Ultimately, further studies are imperative to capitalize on the various applications of bombesin conjugates in both the diagnosis and management of SCLC.
... As nearly half of the patients who presented at a pharmacy had a persistent cough lasting longer than 3 weeks, a chest radiograph could be used to help determine if they had lung cancer (although diagnosis is based on cytology), which is, according to NICE, recommended in a patient experiencing these symptoms [7]. This is significant, as approximately 90 % of patients with lung cancer are symptomatic at the time of diagnosis with the majority of patients having a cough [30]. Our findings are timely as, in England, survival rates of lung cancer are worse in comparison to other European countries. ...
Article
Full-text available
Objectives: We aim to seek expert opinion and gain consensus on the risks associated with a range of prescribing scenarios, preventable using e-prescribing systems, to inform the development of a simulation tool to evaluate the risk and safety of e-prescribing systems (ePRaSE). Methods: We conducted a two-round eDelphi survey where expert participants were asked to score pre-designed prescribing scenarios using a five-point Likert scale to ascertain the likelihood of occurrence of the prescribing event, likelihood of occurrence of harm and the severity of the harm. Results: Twenty four experts consented to participate with fifteen participants and thirteen participants completing rounds 1 and 2 respectively. Experts agreed on the level of risk associated with 136 out of 178 clinical scenarios with 131 scenarios categorised as high or extreme risk. Discussion: We identified 131 extreme or high-risk prescribing scenarios that may be prevented using e-prescribing clinical decision support. The prescribing scenarios represent a variety of categories, with drug-disease contraindications, being the most frequent representing 37 (27%) scenarios and antimicrobial agents being the most common drug class representing 28 (21%) of the scenarios. Conclusion: Our eDelphi study has achieved expert consensus on the risk associated with a range of clinical scenarios with most of the scenarios categorised as extreme or high risk. These prescribing scenarios represent the breadth of preventable prescribing error categories involving both basic and advanced clinical decision support. We will use the findings of this study to inform the development of the e-prescribing risk and safety evaluation tool.
... Çalışmamızda akciğer kanseri semptomları sorgulandı. Literatürde akciğer kanserlerinde ilk semptom ve bulguların sıklığı öksürük (% 8-75), kilo kaybı (% 0-68), dispne (% 3-60), göğüs ağrısı (% 20-49), hemoptizi (% 6-35) olarak verilmektedir (19). Semptomların hiçbiri akciğer kanseri için spesifik olmamakla birlikte sigaranın akciğer kanseri için önemli bir risk faktörü olduğunun vurgulanması ve bu semptomlardan en az bir tanesi olanlara Göğüs Hastalıkları poliklinik kontrolü önerilmesiyle motivasyon sağlandı. ...
Chapter
Lung cancer has been identified as one of the most prevalent causes of illness and death. Lung cancer is also categorized as among the most prevalent types of cancers, along with breast, colorectal, and prostate cancers. Worldwide attempts to manage diseases have remained steady, and lung cancer is expected to remain the primary cause of cancer-related burdens worldwide. The prevalence of lung cancer cases is expected to rise to 3.2 million by 2040. The unpredictable appearance of the 2019 coronavirus disease (COVID-19) has dramatically changed our real lives. This not only has altered our current perspective on life but has also compelled us to redesign how cancer patients should be diagnosed. New studies have also found that the mortality risk of COVID-19 lung cancer patients is larger than that of other cancer patients and that cancer stage has a strong connection with mortality. Further detailed studies are required to strategize treatment plans and to effectively manage the condition.
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Background This study sought to investigate the effects of foam pad balance exercises on balance, physical performance, peripheral neuropathy symptoms, and quality of life in cancer patients undergoing taxane-based chemotherapy. Methods Thirty cancer patients receiving chemotherapy were randomly divided into 2 groups (n = 15/group): control group (CG) and balance exercise group (BG). The BG were asked to perform foam pad balance exercises 60 min/day, twice/week for 6 weeks, along with conventional therapy. The CG only received conventional therapy. The Fullerton Advanced Balance (FAB) Score, Short Physical Performance Battery (SPPB), Michigan Diabetic Neuropathy Score (MDNS), and Functional Assessment of Cancer Therapy-Taxane (FACT-Taxane) were used to assess balance, physical performance, peripheral neuropathy symptoms, and quality of life, respectively, at baseline and after 4 and 6 weeks of treatment. Results At 4 and/or 6 weeks, the CG showed a decline in FAB and SPPB Scores, while the BG maintained their baseline levels. There were significant differences in the FAB Scores between the groups at the 4th and 6th week (p = 0.04 and p < 0.01, respectively) and significant differences in SPPB Scores at only the 6th week (p = 0.03). MDNS showed no significant changes between or within groups. For FACT-Taxane between groups, the CG and BG showed significant decreases (p < 0.01) and increases (p < 0.01), respectively, at 6th week. Conclusions Foam pad balance exercises during chemotherapy can be used to alleviate declining balance and enhance physical performance and quality of life of cancer patients.
Article
Introduction Recent advances in small cell lung cancer (SCLC) treatments necessitate a better understanding of real-world health utility scores (HUS) in patients treated under current standards to facilitate robust pharmaco-economic assessments. Methods In this single institution cohort observational study, HUS were evaluated in patients with SCLC through EQ-5D questionnaires at outpatient visits (encounters). In addition, patients completed questionnaires relating to treatment toxicities and cancer symptoms. Clinical and pathological variables were abstracted from electronic medical records and disease status at each patient visit was documented. The impact of these variables on HUS were explored. Results There were 282 clinical encounters (12% newly diagnosed; 37% stable on treatment; 22% progressing on treatment; 29% stable off therapy/other) in 111 SCLC patients (58% male; 64% extensive stage (ES) SCLC). At the first encounter 29% of patients had an ECOG performance status (PS) ≥ 2. ES-SCLC, bone metastases, female sex, progressive disease and/or PS were each significantly associated with decreased HUS in multivariable analyses. Patients clinically stable on first line therapy had generally steady HUS longitudinally, with differences in HUS between limited disease (LD) and ES patients emerging as treatment progressed. Decreased HUS were associated with increased severity of the majority of measured symptoms (fatigue/tiredness, loss of appetite, pain, drowsiness, shortness of breath, anxiety, depression, and overall well-being; each p<0.001), supporting the value of EQ-5D-derived HUS in assessing health utility. Conclusion Our HUS values in chemotherapy-treated SCLC are clinically relevant and are associated with specific clinico-demographic, symptom and toxicity factors.
Article
Abstract Context: The addition of geftinib to frst-line chemotherapy treatment in EGFR mutated patients may lead to improvement in overall survival in advanced non-small cell lung cancer (NSCLC). Aims: This study aimed to investigate the relationship of epidermal growth factor receptor (EGFR) mutations with clinical features of non-small cell lung cancer patients and to determine overall survival (OS) of EGFR mutated adult NSCLC patients after geftinib treatment. Settings and design: A retrospective observational study was done for 93 advanced NSCLC adult Malaysian patients at Radiotherapy and Oncology Clinic, Hospital Kuala Lumpur, Malaysia. Methods and material: Demographic and medical data were recorded from the patient’s medical record fle. Statistical analysis used: Statistical analysis was performed using SPSS version 21.0. Kaplan-Meier, log-rank test and Cox regression analysis have been performed. Results: There were 93 adult NSCLC Malaysian patients who were examined for EGFR gene mutations. Approximately 35.48% (33/93) of the patients were detected to have EGFR mutations in their tumour tissue DNA. EGFR mutations were commonly observed in females, adenocarcinoma, non-smokers, stage IV NSCLC and patients taking frst-line geftinib treatment. Positive EGFR status of adult NSCLC patients was independently associated with intake of geftinib therapy. There were 19 patients who received 250 mg/day geftinib as the frst-line treatment. The patients with positive EGFR status had increased median survival time as compared than those with negative EGFR status (834.863 vs 246 days). Conclusions: Advanced NSCLC patients with mutated EGFR had a longer median survival time after frst- line geftinib treatment. EGFR mutation is an independent prognostic factor for adult NSCLC patients. Keywords: non-small cell lung cancer, EGFR, survival, geftinib
Article
The stated purpose of this immense compendium is to "be a resource for quick, practical information" for all kinds of physicians taking care of patients with neurological disease. Johnson enlisted the help of no fewer than 115 collaborators, most (but not all) who fit his description of being experts with interest and experience in the specific disease or condition they are asked to discuss.There is, of course, much variation in the quality of the different sections (95, almost as many as there are authors). Most of the authors have restricted themselves to the description of various therapeutic modalities, with only a minimum of absolutely necessary background, but some believe it necessary to be more discursive, usually at the cost of shedding more confusion than light.It is indeed true that during the past several decades neurology has evolved from a descriptive, almost contemplative discipline to one that may, in