Signature: © Pol J Radiol, 2014; 79: 210-218
DOI: 10.12659/PJR.890103
ORIGINAL ARTICLE
Received: 2013.11.25
Accepted: 2014.03.05
Published: 2014.07.18
The assessment of the role of baseline low-dose CT scan
in patients at high risk of lung cancer
Authors’ Contribution:
A Study Design
B Data Collection
C Statistical Analysis
D Data Interpretation
E Manuscript Preparation
F Literature Search
G Funds Collection
Katarzyna Kołaczyk1 ABDEF, Anna Walecka1 AE, Tomasz Grodzki2 BD,
Jacek Alchimowicz2 BD, Andrzej Smereczyński3 AE, Radosław Kiedrowicz4 C
1 Department of Diagnostic Imaging and Interventional Radiology PUM, Independent Public Clinical Hospital No. 1, Szczecin,
Poland
2 Clinical Division of Thoracic Surgery PUM, Specialist Hospital, prof. Alfred Sokołowski Scales, Szczecin, Poland
3 Department of Gastroenterology PUM, Independent Public Clinical Hospital No. 1, Szczecin, Poland
4 Department of Cardiology PUM, Independent Public Clinical Hospital No. 2, Szczecin, Poland
Author’s address: Katarzyna Kołaczyk, Department of Diagnostic Imaging and Interventional Radiology PUM, Independent
Public Clinical Hospital No. 1, Szczecin, Poland, e-mail: kolaczyk@radiologia.szczecin.pl
Summary
Background:
Despite the progress in contemporary medicine comprising diagnostic and therapeutic methods,
lung cancer is still one of the biggest health concerns in many countries of the world. The main
purpose of the study was to evaluate the detection rate of pulmonary nodules and lung cancer in
the initial, helical low-dose CT of the chest as well as the analysis of the relationship between the
size and the histopathological character of the detected nodules.
Material/Methods:
We retrospectively evaluated 1999 initial, consecutive results of the CT examinations performed
within the framework of early lung cancer detection program initiated in Szczecin. The project
enrolled persons of both sexes, aged 55–65 years, with at least 20 pack-years of cigarette smoking
or current smokers. The analysis included assessment of the number of positive results and the
evaluation of the detected nodules in relationship to their size. All of the nodules were classified
into I of VI groups and subsequently compared with histopathological type of the neoplastic and
nonneoplastic pulmonary lesions.
Results:
Pulmonary nodules were detected in 921 (46%) subjects. What is more, malignant lesions as well as
lung cancer were significantly, more frequently discovered in the group of asymptomatic nodules of
the largest dimension exceeding 15 mm.
Conclusions:
The initial, low-dose helical CT of the lungs performed in high risk individuals enables detection
of appreciable number of indeterminate pulmonary nodules. In most of the asymptomatic patients
with histopathologically proven pulmonary nodules greater than 15 mm, the mentioned lesions are
malignant, what warrants further, intensified diagnostics.
Keywords:
PDF file:
Lung Cancer • Pulmonary Nodule • Low-Dose CT
http://www.polradiol.com/abstract/index/idArt/890103
Background
Lung cancer is one of the major health problems in many
countries. According to the National Cancer Registry,
140,564 new cases of cancer were reported in Poland in
2010. Lung cancer was the most common type of cancer
in males (14,794 new cases) and the second most common type of cancer in females (6038 new cases). In the
same year, 92,611 cancer-related deaths were recorded; of
210
these, most deaths in both males and females were due to
to lung cancer (16,187 and 6161 deaths, respectively) [1].
The overall survival of patients with lung cancer is related
with the TNM staging of the disease and treatment applied
[2–9]. In stage I cancer, 5-year survival is as high as 67%
while dropping down to 1–3% for stage IV cancer [9–12].
The average 5-year survival rate in all patients is about
13% [13,14]. The growing scale of the problem and, most
of all, high mortality due to lung cancer led to attempts at
© Pol J Radiol, 2014; 79: 210-218
the development of an efficient lung cancer screening test.
An attempt to use cytological examinations of sputum combined with chest X-rays had failed. No positive correlation
between the results of those examinations and the reduction in mortality rates were observed in the studies conducted in the 1970s and 1980s in the US (Johns Hopkins
Medical Institutions, Memorial Sloan-Kettering Cancer
Center, Mayo Clinic) and Czechoslovakia. [15–23].
As part of the rapid advances in imaging diagnostic techniques in the late 20th century, low-dose computed tomography was developed as an alternative to classical radiography in chest imaging. Published results of the studies conducted by the Japanese group from Nagano, the
Japanese Anti-Lung Cancer Association Project and the
New York’s Early Lung Cancer Action Project opened up
opportunities for this diagnostic method to be successfully used in lung cancer screening examinations [22,24–27].
Besides the United states, and Japan, attempts to introduce low-dose CT screening examinations were also made
in other countries, such as Belgium, Canada, Denmark,
France, Germany, Italy or the Netherlands [22,28]. The
first results of randomized trials are quite promising. In
the study conducted by the National Cancer Institute in a
group of 53,454 subjects, a 20.3% reduction in mortality
rates was observed in the group of patients at higher risk of
lung cancer subjected to low-dose CT examinations as compared to the group subjected to chest X-ray examinations
[29–31]. In Poland, similar projects were started in 2008;
multi-directional analysis of results obtained at individual
trial sites is ongoing [11].
Material and Methods
Retrospective analysis included the results of 1999 consecutive baseline low-dose CT chest scans performed in one
of four diagnostic labs in Szczecin, Poland as part of the
early lung cancer detection program. The project recruited
individuals at higher risk of lung cancer, both males and
females, aged 55 to 65, smoking or with the history of
smoking of at least one pack per day for 20 years (packyears). Individuals who met those criteria received a letter
from the Szczecin City Mayor stating the idea of the program and the CT tests as well as providing explanations
to potential subjects’ concerns. Qualification for the program was made by family physicians who also reported
the presence of alarming clinical symptoms, such as cough,
shortness of breath, coughing up blood, subfebrile body
temperatures, hoarse or dysphagia in a special referral
form. Having obtained such referrals, subjects were obliged
to report for a CT scan in one of four labs taking part in
the program. All test results subject to the assessment
were stored in the database of the Screening Test Program
Coordination Center.
The analysis of the collected data involved determination
of the number of positive results along with the assessment
of detected nodular lesions depending on their size. All
nodular lesions (including partially calcified lesions) were
taken into account, regardless of the percentage content
of the solid component and the ground glass component.
Completely calcified nodules were treated as benign lesions
and excluded from the analysis.
Kołaczyk K. et al. – The assessment of the role of baseline low-dose CT scan…
The lesions were classified into the following 6 groups: isolated asymptomatic nodules sized <5 mm (P1), multiple
asymptomatic nodules sized <5 mm (P2), isolated asymptomatic nodules sized 5–15 mm (P3), multiple asymptomatic
nodules sized 5–15 mm (P4), asymptomatic nodules sized
>15 mm (P5), symptomatic nodules sized >15 mm (P6).
When lesions of different sizes were detected in a single
patient, the size of the largest nodule was decisive in classification. Multiple lesions were defined as the presence of
two or more nodules. The analysis included the presence of
enlarged mediastinal lymph nodes.
Patients in whom lesions detected in CT scans required further diagnostic management according to the pre-defined
algorithm were referred to pneumology centers or to the
Clinical Department of Thoracic Surgery of the Pomeranian
University of Medicine in Szczecin for more detailed diagnostics. This allowed to isolate the group of patients with
confirmed cancer and non-cancer lesions in the lungs.
Clinical data including the number and stage of individual
cancers as well as the type of detected non-cancer lesions
were compared to the analysis of tomographic scan results.
The algorithm used in the program was developed on
the basis of the protocols of the International Early Lung
Cancer Action Project (I-ELCAP) and the Nelson study and
included the following guidelines:
1. Asymptomatic nodules sized <5 mm – follow-up CT scan
in 1 year as part of the program (pneumological consultation for more detailed diagnostics in case of multiple
nodules).
2. Asymptomatic nodules sized 5–15 mm – attempt of
14-day antibiotic therapy, follow-up CT scan (financed
from the National Health Fund) after 3 months for size
reassessment. Pneumological consultation in case of progression.. In case of stable or regressing lesions, CT follow-up after 9–12 months as part of the program.
3. Symptomatic or asymptomatic nodules sized
>15 mm – pneumological consultation for more detailed
diagnostics.
In the following years:
a. Lesion of any size with a growing trend – pneumological
consultation for more detailed diagnostics (further management depending on tumor’s volume doubling time [VDT]).
b. For lesions stable as compared to the previous scan, see 1
and 2 (possible waiver of repeated antibiotic therapy).
Data subject to the assessment, collected from the diagnostic labs of Independent Public Clinical Hospital No. 1
in Szczecin (HOSPITAL 1), Marie Curie Independent Public
Provincial Polyclinical Hospital in Szczecin (HOSPITAL 2)
and the Health Care Center of the Ministry of the Interior
and Administration in Szczecin (HOSPITAL 3) were recorded between 01 January through 31 December 2010. In case
of Prof. Alfred Sokolowski Specialist Hospital in SzczecinZdunow (HOSPITAL 4), scans subjected to the analysis were
recorded between 01 April through 31 December 2010.
All chest scans were performed without intravenous contrast administrations using two 64-slice Siemens Somatom
Sensation Cardiac 64 scanners, one 16-slice Hitachi Eclos 16
scanner and one 6-slice Siemens Somatom Emotion 6 scanner.
211
Original Article
© Pol J Radiol, 2014; 79: 210-218
P1 <5 mm, isolated asymptomatic; 26%
P2 <5 mm, multiple asymptomatic; 20.5%
Lymph nodes;
n=88; 4.4%
Nodular lesions;
n=921; 46%
Figure 1. Percentage distribution of the detected
lesions in the analyzed group combined
with percentage distribution of the
nodules with respect to the category they
were selected from.
P3 5−15 mm, isolated asymptomatic; 15.3%
P4 5−15 mm, multiple asymptomatic; 30.4%
P5 >15 mm, multiple asymptomatic; 7%
P6 >15 mm, symptomatic; 0.8%
10%
n=3
1.5%
n=30
16.7%
n=5
44.6%
n=891
53.9%
n=1078
46.6%
n=14
26.7%
n=8
Negative result
Positive result – not verified
Positive result – verified
Figure 2. Percentage distribution of the analyzed group with respect
to the histopathological verification and examination result.
The scanning parameters approved by the provincial consultant in radiology and applied in two labs were as follows: slice thickness: 5 mm; voltage: 120 kV; current: 17
mAs; CTDIvol: 1.31 mGy. In the remaining labs, acquisition parameters were as follows: slice thickness: 5 mm;
voltage: 110 kV; current: 21 mAs; CTDIvol: 1,58 mGy and
slice thickness: 5 mm; voltage: 120 kV; current: 40 mAs;
CTDIvol: 3.2 mGy.
The statistical analysis of the collected data was conducted using STATISTICA 10™ software (StatSoft Inc.) and the
following tests: Shapiro-Wilk’s W-test, Mann-Whitney’s
U-test, Fisher’s test, Pearson’s chi-squared test, Pearson’s
chi-squared test with Yates’ correction. In all tests, statistical significance was defined as p<0.05 while the values
between p=0.05 and p=0.1 were considered to be at the
border of statistical significance.
P3 5−15 mm, isolated asymptomatic
P4 5−15 mm, multiple asymptomatic
P5 >15 mm, asymptomatic
P6 >15 mm, symptomatic
Figure 3. Percentage distribution of the histopathologically verified
pulmonary nodules with respect to the category they were
selected from.
The study group consisted of subjects in the age range of
55–65 years.
The mean age was 59.3±3.03 years (range 55–65). No statistically significant differences were observed in terms of age
(p=0.87) or gender (p=0.57) in respective groups. Nodular
lesions were detected in 921 (46%) subjects. Negative results
were obtained in 1078 (54%) cases. Enlarged lymph nodes
were detected in 88 (4.4%) subjects (Figure 1).
The highest numbers of nodular lesions were detected
in the categories of asymptomatic lesions sized <5 mm
(n=428) (categories P1 and P2) and asymptomatic lesions
sized 5–15 mm (n=421) (categories P3 and P4). In group
P5 (asymptomatic lesions sized >15 mm) 65 lesions were
detected while 7 cases were detected in category P6 (symptomatic lesions sized >15 mm).
Results
The group of subjects qualified to the program of early lung
detection of lung cancer using low-dose computed tomography consisted of 1100 females and 899 males (F/M=1.22).
212
In the study group, asymptomatic multiple nodular lesions
sized <5 mm were statistically significantly more common
in women than in men. No statistically significant correlations between the size of the lesions and the subjects’
Kołaczyk K. et al. – The assessment of the role of baseline low-dose CT scan…
© Pol J Radiol, 2014; 79: 210-218
4.0
Figure 4. Percentage distribution of the
benign lesions with respect to the
histopathological diagnosis.
30.7%
N=4
3.5
3.0
2.5
2.0
1.5
15.4%
N=2
15.4%
N=2
1.0
7.7%
N=1
0.5
0.0
Hamartoma Abscess
7.7%
N=1
7.7%
N=1
7.7%
N=1
7.7%
N=1
Lymph Calcification Tuberculoma Fibrosis Inflammatory Ischemic
node
lesion
lesion
Giant cell carcinoma; N=2; 20%
Figure 5. Percentage distribution of the detected
lung cancers with respect to their
histopathological type.
Planoepithelial carcinoma; N=2; 20%
Small cell carcinoma;
n=4; 29%
Non-small cell
carcinoma;
N=10; 71%
Adenocarcinoma; N=6; 60%
gender were detected in the remaining groups. Enlarged
lymph nodes were statistically significantly more common
in males.
lesions (14 out of 17 cases) and in 47% of all verified cases
(14 out of 30 cases), accounting for 0.7% of the entire study
population.
Histopathological examination was performed in 30 nodular lesions, accounting for 3% of patients with positive
results and 1.5% of the entire study population. Figure 2
presents the percentage distribution of the study population depending on the scan result and histopathological
verification, if performed.
In the group of histopathologically verified cases, both
overall malignant lesions and lung cancer cases were significantly more common in cases of asymptomatic lesions
sized >15 mm (p=0.008 and p=0.03, respectively). No statistically significant correlations between the size of the
lesions and the nature of neoplastic growth were detected
in the remaining groups.
Figure 3 illustrates the percentage distribution of histopathologically verified lesions depending on the group of
patients from whom the lesions were isolated.
Benign lesions were diagnosed in 43% of histopathologically verified cases (13 out of 30 lesions). Enlarged lymph
nodes were detected in 1 case. Figure 4 presents the percentage distribution of benign lesions depending on the histopathological examination result.
In the group of nodular lesions subjected to histopathological examination, 57% of lesions were assessed as malignant
(17 out of 30 cases), including 14 cases lung cancer, 1 case
of malignant mesothelioma, 1 kidney cancer metastasis
and 1 sarcoma metastasis. Lung cancer was confirmed in
82% of histopathologically confirmed cases of malignant
In the group of histopathologically confirmed malignant
lung cancers, non-small lung cell carcinoma accounted
for 71% of diagnoses (10 out of 14 cases). In the remaining 29% of verified cases (4 out of 14 cases), small lung cell
carcinoma was detected. In the group of subjects with confirmed lung cancer, 6 cases (43%) were assessed as clinical
stage I, 1 case each (7%) was assessed as clinical stage II
and IV, and 6 cases (43%) were assessed as clinical stage III.
Figure 5 presents the percentage distribution of diagnosed
lung cancers depending on histological type.
In the group of subjects with CT-diagnosed nodular lesions
subsequently verified by histopathological examination,
inoperable lung cancer was significantly more common in
males (p-0.043).
213
Original Article
Figure 6. Sarcoma metastasis. Nodule with spiculated margins in 2
segment of the right lung. Category P4 lesion.
In the group of subjects with histopathologically verified
lesions (n=30), enlarged lymph nodes were detected in 7
individuals, including 1 case of enlarged lymph nodes
accompanying a benign lesion and 6 cases of enlarged
lymph nodes accompanying malignant lesions (Figures 6
and 7).
Discussion
To date, no final conclusions were drawn as pertains the
impact of screening tests on the reduced mortality rates
in lung cancer; however, the preliminary results appear
quite optimistic [29,32–36]. For sure, low-dose computed
tomography increases the detection rate of early forms of
lung cancer, as confirmed by authors of numerous publications [11,15,24,26,33,37,38]. Also promising are the results
of the study conducted by the National Cancer Institute in
a group of 53,454 subjects, showing a 20.3% reduction in
mortality rates was observed in the group of patients at
higher risk of lung cancer subjected to low-dose spiral CT
examinations as compared to the group subjected to chest
X-ray examinations [29–31,34]. Unfortunately, the preliminary results also suggest numerous problems that have to
be addressed before this diagnostic technique is used at
larger scale.
At our Szczecin site, 14 cases of lung cancer were detected
on the basis of 1999 baseline screening chest scans (0.7%),
including 6 cases (43%) diagnosed as clinical stage 1 cancer. The results were submitted to statistical analysis that
revealed no significant differences in gender and age with
relation to the diagnostic site.
Kaneko et al. published data obtained in the project conducted under the auspices of Anti-Lung Cancer Association
(ALCA), involving 3457 low-dose CT scans performed in
1369 patients between September 1993 and April 1995.
Fifteen (0.4%) cases of lung cancer were detected, including
14 cases (93%) of stage I cancer; the average tumor density was 16 mm [26]. Sone et al. reported that a lung cancer screening program conducted in years 1996-1998 using
low-dose computed tomography involved 13786 scans performed in 5483 subjects. Sixty (0.4%) cases of lung cancer
were detected, including 55 cases (92%) of stage I cancer;
the average tumor density was 13.4 mm [26]. Henschke
214
© Pol J Radiol, 2014; 79: 210-218
Figure 7. Giant cell carcinoma located in the right upper lobe of the
lung. Category P5 lesion.
et al. published the preliminary results of the Early Lung
Cancer Action Project (ELCAP), that included 1000 high risk
subjects. A total of 27 (2.7%) cancer cases were diagnosed,
including 23 (85%) at the earliest stage [20,24,26].
The morbidity rate in the project by Henschke et al. (2.7%)
was higher than that observed by the Japanese researchers
Kaneko et al. and Sone et al. (0,4%). This might be explained
by the differences in the incidence of lung cancer in different countries. Lung cancer is nearly twice as common
in the US compared to Japan [26]. However, discrepancies
in the results of screening tests may not be always due to
epidemiological factors. In a program of early low-dose CT
detection of asymptomatic lung cancers conducted in 817
asymptomatic German smokers by Diederich et al., lung
cancer was diagnosed in 11 subjects, which corresponded to the morbidity rate of 1.3% [39]. Using an algorithm
similar to that proposed by Henschke et al., the authors
observed a lower morbidity rate. This appears to be due
not only to the age differences between the study groups,
but also to the differences in acquisition parameters. Our
study does not account for the results of follow-up scans,
which makes it impossible to carry out a precise analysis of
morbidity in comparison to the literature data.
When analyzing worldwide reports, one may be struck by
the lack of unanimity in screening algorithms [24,26,39–42]
which with no doubt has an effect on the obtained results.
However, it should be kept in mind that examinations
using low-dose CT are still in the exploratory phase.
In the results of the cited studies, the percentages of malignant lung tumors detected at clinical stage I was high and
ranged from 85% in the ELCAP project to about 90% in the
projects conducted by the Japanese researchers [24,26]. At
our Szczecin site, 43% of cancers were diagnosed as clinical
stage I, and 43% of cancers were diagnosed as clinical stage
III between 1 January and 31 December 2010. However,
extensive research to identify an optimum screening test
have been conducted in the US and Japan for about 40
years [17,19,21,22,23]. In Poland, no large scale attempts to
introduce alternative chest imaging forms have been made
after cessation of the program of miniature mass X-rays in
the 1980s. Therefore, most cases of lung cancers detected
in our country are either symptomatic or detected accidentally when performing other diagnostic examinations [11].
© Pol J Radiol, 2014; 79: 210-218
Compared to non-European researchers, Diederich et al.
observed a decidedly lower percentage of clinical stage I
tumors (58%) [39]. Considering the fact that the algorithm
used by Diederich et al. was similar to that used in the
ELCAP program and that the final report included also the
follow-up examinations, this result was not significantly
different from the results of our study, considering the fact
that only baseline scans were included in our analysis.
In our study, the presence of nodular lesions was demonstrated in 921 (46%) program subjects while also observing
that multiple asymptomatic nodules smaller than 5 mm
were significantly more common in women. No statistical
differences were observed between the age of the subjects
and the lesions detected in CT scans. Similar results were
obtained by Diederich et al. who observed the presence of
nodules in 50% of subjects with to statistically significant
differences with regard to subjects’ gender and age [39]. The
higher incidence of nodules smaller than 5 mm in female
subjects might be due to the fact that a higher number of
women was enrolled in the program in Szczecin within the
period of interest as compared to the number of man (55%
vs. 45%). The obtained result seems to be of no importance
in the aspect of management algorithms being used as the
probability of malignancy of nodules smaller than 5 mm is
estimated by different authors at about 1% [43,44].
In the Szczecin program, multiple asymptomatic nodular lesions sized 5 to 15 mm were diagnosed in the largest number of participants (n=280). The second most
populated group (n=239) was the group of subjects with
single asymptomatic nodular lesions not larger than 5 mm.
Regardless of the program and percentage ratios, lesions
with largest dimensions not exceeding 4 or 5 mm and nodules within the next size category, usually not exceeding
10 mm, constituted the largest groups of study subjects,
which appears to be consistent with our observations
while ignoring the methodological differences [24,39]. Of
note is the fact that individual projects differed in nodule
size threshold values [24,39,45]. This is important from
the standpoint of the assumed guidelines as management
regimens for individual groups of nodules differed largely
depending on their size. Larger lesions require more aggressive strategies associated with additional financial demand
and increased risk of complications in patients undergoing
invasive procedures [43,46]
Another important problem associated with lung cancer
screening program guidelines is associated with the determination of the optimum level above which the risk of
malignant lesions is significantly elevated. In our study, we
observed that in the group subjected to histopathological
verification both lung cancer and malignant lesions were
statistically more common among asymptomatic nodules
larger than 15 mm. It is impossible to overlook discrepancies in data reported in worldwide literature on this subject [24,26,42]. It is however indisputable that the likelihood of malignancy of nodular lesions is directly proportional to their size [43]. Wahidi et al. estimated that the risk
of malignancy is 0–1% for lesions sized <5 mm, 6–28% for
lesions sized 5–10 mm, 41–64% for lesions sized 1–2 cm and
67–82% for lesions sized 2–3 cm [47,48]. Therefore, in order
to meet the primary condition of curing the cancer, i.e. to
Kołaczyk K. et al. – The assessment of the role of baseline low-dose CT scan…
detect the tumor at the possibly earliest stage, it is legitimate to search for lesions large enough to be resectable and
small enough to avoid false positive results.
Unfortunately, due to the population being too small, it
was impossible to conduct a reliable analysis of correlations between the nature of lesions and their size in the
group of symptomatic patients diagnosed with lesions sized
>15 mm. Out of 6 subjects, only 3 could be definitely diagnosed. Other two subjects resigned of further diagnostic
tests while one subject suffered severe cerebrocranial injury as a result of traffic accident.
Besides the assessment of size, evaluation of lesion morphology is also important in radiological examinations[44,49–53]. Initially, majority of algorithms used in
screening for lung cancer was designed only on the basis
of size parameters. Only few authors included structural
criteria in their programs [41]. Data obtained in individual
screening tests allowed to modify the management algorithm proposed in 2005 by the Fleischner Society, as evidence by guidelines published for example in the US, Japan
and France and making diagnostic algorithms dependent on
the morphology of lesions [28,54,55].
Introduction of spiral computed tomography led to an
increase in the number of small nodular lesions detected
in lungs [38,56,57]. Higher sensitivity of this method compared to radiography was documented in numerous articles
[2,12,18,21,43,58–60]. Unfortunately, a large part of lesions
detected in the scans are of ambiguous clinical nature, and
differentiation of benign and malignant lesions remains a
challenge for radiologists [32,43,44,56,57,61–64]. In addition, computed tomography is most helpful in detecting
peripheral parenchymal nodules, while its usefulness in
case of lesions located in direct vicinity of pulmonary hila
or within the bronchopulmonary tree is lower and cannot be compared to such diagnostic methods as cytological
examination of sputum combined with autofluorescence
bronchoscopy [13,31,41]. According to literature data, noncalcified nodules in pulmonary parenchyma are detected in
9-66% of patients, with as much as 88-99% of these lesions
being of benign character [65]. Other imaging techniques,
such as contrast-enhanced computed tomography, dynamic
magnetic resonance imaging and FDG PET proved helpful
in differentiating unspecified lung nodules [52,61,63,64,66–
69]. However, also these methods are of limited use in evaluating lesions not larger than 10 mm, associated with the
largest number of controversies as regards the management
algorithms [44,56,57,61–63]. In addition, the value of FDG
PET in differentiating ground glass lesions and mixed type
lesions is lower than that of solid lesions, and false positive
results may be observed in patients with active tuberculosis, histoplasmosis or rheumatic diseases [61].
The lesion volume doubling time is another factor helpful
in differentiating benign and malignant nodular lesions
[11,49,61,64,65,70]. Benign lesions grow rapidly or very
slowly, in contrast to malignant lesions which present an
intermediate rate of growth, depending on their histological type [61,64,65,70]. Some authors assume that stability of lesion image over a period of two years suggests
its benign character [64,69–71]. However, there are also
215
Original Article
supporters of a theory suggesting the need for further
follow up of lesions, particularly small nodules of slow
growth rate [50,52,56,61,64]. Currently it is assumed that
most malignant pulmonary lesions doubles their volume
in periods of 20 to 400 days [64]. However, the parameter may have different value depending on the morphology of lesions. Hasegawa et al. observed that the average
volume doubling time in case of ground glass, partially
solid (mixed) and solid lesions was 813, 457 and 149 days,
respectively [43,59,72]. Our study does not account for the
results of follow-up examinations, thus making it impossible to assess the rate of lesion growth. However, the primary objective of our analysis was related to the overall data
provided by the baseline low-dose chest CT scan.
In screening examinations, assessment of lymph nodes
is difficult due to the contrast agent not being administered. With thus-designed protocols, radiologists must
keep in minds the anatomical variants that might resemble lymphadenopathy [73]. In our study, enlarged mediastinal lymph nodes were diagnosed in 88 subjects, with the
incidence being significantly higher in males. This might
be associated with our other observation that inoperable,
more advanced stages of cancer were also diagnosed more
frequently in males. In addition, on the basis of data analyzed in our study, enlarged lymph nodes were observed
in 5 out of 14 subjects with histopathologically confirmed
lung cancer. In these 5 patients, only 1 had the tumor at
the earliest stage of development. The remaining 4 program
participants were diagnosed with lung cancer at clinical
stages III and IV. It should be kept in mind that CT scans
became the best measure of lymph node volume with significant limitations regarding the analysis of node conditions. The relatively low sensitivity (41–67%) and low specificity (79–86%) of this technique are due to the fact that
lymph nodes may be in inflammatory condition, particularly in patients with secondary pneumonia, while lymph
nodes of normal size may contain cancer cells [70,71].
Microscopic cancer involvement of normal-size lymph
nodes was observed in 5–64% of cases while 15–30% of
enlarged lymph nodes were free of cancer cells [70].
When analyzing our program results it should be assumed
that following the examination performed as part of the
early lung cancer detection program some patients resigned
of further diagnostics aimed at elucidation of the nature
of their lesions or presented for attempted treatment at
another site in Poland. However, considering that the
Clinical Department of Thoracic Surgery of the Pomeranian
University of Medicine in Szczecin is the only regional
center performing lung cancer surgeries and offering its
services also to the residents of Lubuskie Province, such
likelihood appears to be very low [11].
All examinations, results of which have been presented in this study were carried out in 4 diagnostic labs in
Szczecin and subsequently analyzed by different radiologists. Therefore, there is a possibility of discrepancies in
the assessments of CT scans provided by different physicians. Leader et al. conducted a study to assess the consistency in the detection of nodular lesions between radiologists analyzing low-dose CT scans [74]. The presented
216
© Pol J Radiol, 2014; 79: 210-218
results demonstrated low degree of consensus between the
assessing physicians which, according to the authors, could
be corrected by using computer-assisted assessment of CT
scans [74,75]. With no doubt, results of the increasing number of papers on Computer Aided Diagnosis (CAD) of nodular lesions require that their widespread use should be considered [31,32,37,43,74–76]. According to some researchers,
due to the fact that the assessment of screening tests is
much work-consuming, the algorithm should be used as the
second, independent assessing entity along with the radiologist [31,75]. This would allow to reduce the number of
false negative results [75].
Not all diagnostic labs used identical acquisition parameters. Slight differences were observed mainly in currents,
and thus in the volumetric dose index CTDIvol. To date, no
consensus has been achieved in relation to minimum clinically acceptable scanning parameters [77], Studies assessing the capabilities of low-dose computed tomography in
detection of lung nodules demonstrated that currents in the
range of 20–50 mAs were sufficient for the analysis of this
type of lesions [77]. This fact was made use of when designing long cancer screening tests; it should be mentioned that
the acquisition parameters differed slightly in individual
programs [24,39]. Based on the above criteria, it appears
that the differences in these parameters should not have a
significant impact on the final results of the examinations
included in the analysis.
Spiral computed tomography is more sensitive than conventional radiography, and the possibility to use lower
exposure doses makes it acceptable from the standpoint
of radiological protection in screening tests [21,37,59].
However, only the results of trials assessing the primary
endpoint, i.e. the mortality rate shall determine whether the method should be considered most efficient in the
early diagnostics of lung cancer [2]. Numerous trials conducted to date revealed a large number of problems that
have to be addressed before final decisions can be made
[10,32,35,43,52,78,79]. Most controversies are related to
the high rate of false positive results, particularly in cases
of tiny nodular lesions, leading to unnecessary invasive
interventions, excess burden to health care systems and
excess costs [32,43,78]. In addition, standardization of diagnostic management algorithms that take into account e.g.
financial capabilities of health care systems in individual
states, is required [27]. However, one may expect that such
a large study group combined with the large amount of
data already collected will in near future allow to precisely
determine the positive impact of low-dose spiral CT tests
on long-term survival.
Conclusions
1. Screening low-dose spiral CT chest scans in patients at
high risk of lung cancer allows to detect a significant
number of nodular lesion of ambiguous clinical nature.
2. In most asymptomatic patients with lung nodules with
diameters larger than 15 mm as revealed in this study
and subsequently verified by histopathological examination, the lesions were of malignant character requiring
more detailed diagnostic examinations.
© Pol J Radiol, 2014; 79: 210-218
Kołaczyk K. et al. – The assessment of the role of baseline low-dose CT scan…
References:
1. Wojciechowska U, Didkowska J, Zatoński W: Nowotwory złośliwe w
Polsce w 2010 roku. 2012. ISSN 0867-8251 [in Polish]
2. Black WC: Unexpected observations on tumor size and survival in
stage IA non-small cell lung cancer. Chest, 2000; 117: 1532–34
3. Chirikos TN, Hazelton T, Tockman M et al: Screening for lung cancer
with CT: a preliminary cost-effectiveness analysis. Chest, 2002; 121:
1507–14
4. Flieder DB, Port JL, Korst RJ et al: Tumor size is a determinant of
stage distribution in t1 non-small cell lung cancer. Chest, 2005; 128:
2304–8
5. Janssen-Heijnen MLG, Coebergh JWW: Trends in incidence and
prognosis of the histological sybtypes of lung cancer in North
America, Australia, New Zealand and Europe. Lung Cancer, 2001; 31:
123–37
6. Port JL, Kent MS, Korst RJ et al: Tumor size predicts survival within
stage IA non-small cell lung cancer. Chest, 2003; 124: 1828–33
7. Wisnivesky JP, Yankelevitz D, Henschke CI: Stage of lung cancer in
relation to its size: part 2. Evidence. Chest, 2005; 127: 1136–39
8. Wisnivesky JP, Yankelevitz D, Henschke I: The effect of tumor size
on curability of stage I non-small cell lung cancers. Chest, 2004; 126:
761–65
9. Xiong Z, Xiong G, Man Y et al: Detection of lung cancer by oral
examination. Medical Hypotheses, 2010; 74: 346–47
10. Getman VV, Mueller MR: Epidemiology (incidence, survival), risk
factors, prevention (screening). Eur Surg, 2004; 36: 61–65
11. Grodzki T, Walecka A, Fabian W et al: Program wczesnego
wykrywania nowotworów płuc za pomocą tomografii komputerowej
– wstępne doświadczenia Szczecina. Pneumonol Alergol Pol, 2009;
77: 521–27 [in Polish]
26. Sobue T, Moriyama N, Kaneko M et al.: Screening for lung cancer
with low-dose helical computed tomography: Anti-Lung Cancer
Association Project. J Clin Oncol, 2002; 20: 911–20
27. Wisnivesky JP, Mushlin AI, Sicherman N et al: The cost-effectiveness
of low-dose CT screening for lung cancer: preliminary results of
baseline screening. Chest, 2003; 124: 614–21
28. Couraud S, Cortot AB, Greillier L et al: From randomized trials to the
clinic: is it time to implement individual lung-cancer screening in
clinical practice? A multidisciplinary statement from French experts
on behalf of the french intergroup (IFCT) and the groupe d’Oncologie
de langue française (GOLF). Ann Oncol, 2013; 24: 586–97
29. Aberle DR, Adams AM, Berg CD et al: Reduced lung-cancer mortality
with low-dose computed tomographic screening. N Engl J Med,
2011; 395–409
30. Statement concerning the National Lung Screening Trial
[online].2008.[dostęp: 02 marca 2012].Dostępny w Internecie: http://
www.cancer.gov/images/dsmb-nlst.pdf
31. White CS.: National Lung Screening Trial: a breakthrough in lung
cancer screening? J Thorac Imaging, 2011; 26: 86–87
32. Boiselle PM, Ernst A, Karp DD: Lung cancer detection in the
21st century: potential contributions and challenges of emerging
technologies. Am J Roentgenol, 2000; 175: 1215–21
33. Jett JR, Midthun DE: Screening for lung cancer: current status
and future directions: Thomas A. Neff lecture. Chest, 2004; 125 (5
Suppl.): 158S–62S
34. Mulshine JL, van Klaveren RJ: Lung cancer screening: what is the
benefit and what do we do about it? Lung Cancer, 2011; 71: 247–48
35. Ravenel JG, Costello P, Silvestri GA: Screening for lung cancer. Am J
Roentgenol, 2008; 190: 755–61
12. Swensen SJ, Jett JR, Hartman TE et al: Lung cancer screening with
CT: Mayo Clinic experience. Radiology, 2003; 226: 756–61
36. Warner E, Jotkowitz A, Maimon N: Lung cancer screening-are we
there yet? Eur J Intern Med, 2010; 21: 6–11
13. Lam B, Lam SY, Wong MP et al: Sputum cytology examination
followed by autofluorescence bronchoscopy: A practical way of
identifying early stage lung cancer in central airway. Lung Cancer,
2009; 64: 289–94
37. Diederich S, Wormanns D: Impact of low-dose CT on lung cancer
screening. Lung Cancer, 2004; 45 (Suppl.2): S13–19
14. Ruano-Ravina A, Figueiras A, Barros-Dios JM: Lung cancer and
related risk factors: an update of the literature. Public Health, 2003;
117: 149–56
39. Diederich S, Wormanns D, Semik M et al: Screening for early lung
cancer with low-dose spiral CT: prevalence in 817 asymptomatic
smokers. Radiology, 2002; 222: 773–81
15. Bach PB, Kelley MJ, Tate RC et al: Screening for lung cancer: a
review of the current literature. Chest, 2003;123(1 Suppl.): 72S–82S
40. Lopes Pegna A, Picozzi G, Mascalchi M et al: Design, recruitment and
baseline results of the ITALUNG trial for lung cancer screening with
low-dose CT. Lung Cancer, 2009; 64: 34–40
16. Bach PB, Silvestri GA, Hanger M et al: Screening for lung cancer:
ACCP evidence-based clinical practice guidelines (2nd ed.). Chest,
2007; 132(3 Suppl.): 69S–77S
17. Doria-Rose VP, Marcus PM, Szabo E et al: Randomized controlled
trials of the efficacy of lung cancer screening by sputum cytology
revisited: a combined mortality analysis from the Johns Hopkins
Lung Project and the Memorial Sloan-Kettering Lung Study. Cancer,
2009; 115: 5007–17
18. Dziadziuszko R: Leczenie drobnokomórkowego raka płuca – zalecenia
European Society for Medical Oncology (ESMO) z 2010 roku. Med
Prakt, 2012; (1): 73–76 [in Polish]
38. Ganti AK, Mulshine JL: Lung cancer screening. Oncologist, 2006; 11:
481–87
41. Menezes RJ, Roberts HC, Paul NS et al: Lung cancer screening using
low-dose computed tomography in at-risk individuals: the Toronto
experience. Lung Cancer, 2010; 67: 177–83
42. Nawa T, Nakagawa T, Kusano S et al: Lung cancer screening using
low-dose spiral CT: results of baseline and 1-year follow-up studies.
Chest, 2002; 122: 15–20
43. MacMahon H, Austin JH, Gamsu G et al: Guidelines for management
of small pulmonary nodules detected on CT scans: a statement from
the Fleischner Society. Radiology, 2005; 237: 395–400
19. Melamed MR, Flehinger BJ, Zaman MB et al: Screening for early lung
cancer. Results of the Memorial Sloan-Kettering study in New York.
Chest, 1984; 86: 44–53
44. Xu DM, van der Zaag-Loonen HJ, Oudkerk M et al: Smooth or
attached solid indeterminate nodules detected at baseline CT
screening in the NELSON study: cancer risk during 1 year of followup. Radiology, 2009; 250: 264–72
20. Rossi A, Maione P, Colantuoni G et al: Screening for lung cancer: New
horizons? Crit Rev Oncol Hematol, 2005; 56: 311–20
45. Swensen SJ: CT screening for lung cancer. Am J Roentgenol, 2002;
179: 833–36
21. Roszkowski K: Komentarz do artykułu T. Grodzkiego i wsp. “Program
wczesnego wykrywania nowotworów płuc za pomocą tomografii
komputerowej – wstępne doświadczenia Szczecina”. Pneumonol
Alergol Pol, 2009; 77: 571–72 [in Polish]
46. Alberts WM: Diagnosis and management of lung cancer executive
summary: ACCP evidence-based clinical practice guidelines (2nd ed.).
Chest, 2007; 132(3 Suppl.): 1S–19S
22. Sagawa M, Usuda K, Aikawa H et al: Lung cancer screening and its
efficacy. Gen Thorac Cardiovasc Surg, 2009; 57: 519–27
23. Sanderson DR: Lung cancer screening: the Mayo study. Chest, 1986;
89: 324S
24. Henschke CI, McCauley DI, Yankelevitz DF et al: Early Lung Cancer
Action Project: overall design and findings from baseline screening.
Lancet, 1999; 354: 99–105
25. Mazzone PJ: Lung cancer screening: an update, discussion, and look
ahead. Curr Oncol Rep, 2010; 12: 226–34
47. Austin JH: The incidental small pulmonary nodule and the
Fleischner criteria 5 years later: have we learned anything more? J
Thorac Imaging, 2011; 26: 88–89
48. Brandman S, Ko JP: Pulmonary nodule detection, characterization,
and management with multidetector computed tomography. J
Thorac Imaging, 2011; 26: 90–105
49. Libby DM, Smith JP, Altorki NK et al: Managing the small pulmonary
nodule discovered by CT. Chest, 2004; 125: 1522–29
50. Ohta Y, Shimizu Y, Kobayashi T et al: Pathologic and biological
assessment of lung tumors showing ground- glass opacity. Ann
Thorac Surg, 2006; 81: 1194–98
217
Original Article
51. Henschke CI, Yankelevitz DF, Mirtcheva R et al: CT screening for
lung cancer: frequency and significance of part-solid and nonsolid
nodules. Am J Roentgenol, 2002; 178: 1053–57
52. Wahidi MM, Govert JA, Goudar RK et al: Evidence for the treatment
of patients with pulmonary nodules: when is it lung cancer?: ACCP
evidence-based clinical practice guidelines (2nd ed.). Chest, 2007; 132
(3 Suppl.): 94S–107S
53. Lee HY, Lee KS: Ground-glass opacity nodules: histopathology,
imaging evaluation, and clinical implications. J Thorac Imaging,
2011; 26: 106–18
54. Jacobson FL, Austin JHM, Field JK et al: Development of The
American Association for Thoracic Surgery guidelines for lowdose computed tomography scans to screen for lung cancer in
North America: Recommendations of The American Association
for Thoracic Surgery Task Force for Lung Cancer Screening and
Surveillance. J Thorac Cardiovasc Surg, 2012; 144: 25–32
55. Guidelines for the management of pulmonary nodules detected
by low-dose CT lung cancer screening [online]. 2013. [Access:
23 November 2013]. http://jscts.org/pdf/guideline/gls3rd_
english130621.pdf.
56. Benjamin MS, Drucker EA, McLoud TC et al: Small pulmonary
nodules: detection at chest CT and outcome. Radiology, 2003; 226:
489–93
57. Jeudy J, White CS, Munden RF et al: Management of small
(3–5-mm) pulmonary nodules at chest CT: global survey of thoracic
radiologists. Radiology, 2008; 247: 847–53
58. Erasmus JJ, Connolly JE, McAdams HP et al: Solitary pulmonary
nodules: Part I. Morphologic evaluation for differentiation of benign
and malignant lesions. Radiographics, 2000; 20: 43–58
© Pol J Radiol, 2014; 79: 210-218
64. Yankelevitz DF, Henschke CI: Does 2-year stability imply that
pulmonary nodules are benign? Am J Roentgenol, 1997; 168: 325–28
65. Takashima S, Sone S, Li F et al: Indeterminate solitary pulmonary
nodules revealed at population- based CT screening of the lung: using
first follow- up diagnostic CT to differentiate benign and malignant
lesions. Am J Roentgenol, 2003; 180: 1255–63
66. Lowe VJ, Fletcher JW, Gobar L et al: Prospective investigation of
positron emission tomography in lung nodules. J Clin Oncol, 1998;
16: 1075–84
67. Silva CT, Amaral J, Moineddin R et al: CT characteristics of lung
nodules present at diagnosis of extrapulmonary malignancy in
children. Am J Roentgenol, 2010; 194: 772–78
68. Swensen SJ, Brown LR, Colby TV et al: Pulmonary nodules: CT
evaluation of enhancement with iodinated contrast material.
Radiology, 1995; 194: 393–98
69. Takashima S, Sone S, Li F et al: Small solitary pulmonary nodules
(£1 cm) detected at population-based CT screening for lung cancer:
reliable high-resolution CT features of benign lesions. Am J
Roentgenol, 2003; 180: 955–64
70. Prokop M, Galanski M: Spiralna i wielorzędowa tomografia
komputerowa człowieka. 2007. ISBN 978-83-89769-23-7 [in Polish]
71. Webb WR: Radiologic evaluation of the solitary pulmonary nodule.
Am J Roentgenol, 1990; 154: 701–8
72. Hasegawa M, Sone S, Takashima S et al: Growth rate of small lung
cancers detected on mass CT screening. Br J Radiol, 2000; 73:
1252–59
73. Glazer HS, Aronberg DJ, Sagel SS: Pitfalls in CT recognition of
mediastinal lymphadenopathy. Am J Roentgenol, 1985; 144: 267–74
59. Li F, Sone S, Abe H et al: Low-dose computed tomography screening
for lung cancer in a general population: characteristics of cancer in
non-smokers versus smokers. Acad Radiol, 2003; 10: 1013–20
74. Leader JK, Warfel TE, Fuhrman CR et al: Pulmonary nodule
detection with low-dose CT of the lung: agreement among
radiologists. Am J Roentgenol, 2005; 185: 973–78
60. Strauss GM., Dominioni L, Jett J.R., et al.: Como international
conference position statement: lung cancer screening for early
diagnosis 5 years after the 1998 Varese conference. Chest 2005;127:
1146–51
75. Das M, Mühlenbruch G, Heinen S et al: Performance evaluation of
a computer-aided detection algorithm for solid pulmonary nodules
in low-dose and standard-dose MDCT chest examinations and its
influence on radiologists. Br J Radiol, 2008; 81: 841–47
61. Erasmus JJ, McAdams HP, Connolly JE: Solitary pulmonary nodules:
Part II. Evaluation of the indeterminate nodule. Radiographics, 2000;
20: 59–66
76. Oda S, Awai K, Murao K et al: Computer-aided volumetry of
pulmonary nodules exhibiting ground-glass opacity at MDCT. Am J
Roentgenol, 2010; 194: 398–406
62. Markowitz SB, Miller A, Miller J et al: Ability of low-dose helical
CT to distinguish between benign and malignant noncalcified lung
nodules. Chest, 2007; 131: 1028–34
77. Kubo T, Lin P-J P, Stiller W et al: Radiation dose reduction in chest
CT: a review. Am J Roentgenol, 2008; 190: 335–43
63. Schaefer JF, Vollmar J, Schick F et al: Solitary pulmonary nodules:
dynamic contrast-enhanced MR imaging-perfusion differences in
malignant and benign lesions. Radiology, 2004; 232: 544–53
218
78. Lee CI, Forman HP: CT screening for lung cancer: implications on
social responsibility. Am J Roentgenol, 2007; 188: 297–98
79. Parkin DM, Moss SM: Lung cancer screening: improved survival but
no reduction in deaths – the role of “ overdiagnosis”. Cancer, 2000;
89: 2369–76