Original Article

Prognostic effects of preoperative obstructive pneumonitis or

atelectasis and comparison with tumor size in non-small cell lung
cancer
Zhaofei Pang1*, Nan Ding1*, Wei Dong2, Yang Ni3, Tiehong Zhang3, Xiao Qu1, Jiajun Du1,2, Qi Liu1
1
Institute of Oncology, 2Department of Thoracic Surgery, 3Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong
University, Jinan 250021, China
Contributions: (I) Conception and design: J Du, Q Liu, Z Pang; (II) Administrative support: J Du, Q Liu, W Dong; (III) Provision of study materials
or patients: Y Ni, T Zhang; (IV) Collection and assembly of data: N Ding, Z Pang; (V) Data analysis and interpretation: N Ding, W Dong, Y Ni, T
Zhang; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.
*These authors contributed equally to this work.
Correspondence to: Jiajun Du. 324 Jingwu Road, Jinan 250021, China. Email: [email protected]; Qi Liu. 324 Jingwu Road, Jinan 250021, China.
Email: [email protected].

Background: In the eighth TNM staging system proposal, lung cancer with part or complete obstructive
pneumonitis/atelectasis was classified to T2 category, and dividing lines of T category were changed. We
conducted this study to search prognostic effect of preoperative obstructive pneumonitis/atelectasis and its
comparison with tumor size.
Methods: We collected clinical characteristics, preoperative hematological indicators, follow-up
information of 1,313 lung cancer patients. Chi-square test was used to search relationship between
obstruction pneumonitis/atelectasis and other factors. Kaplan-Meier (K-M) curves and cox regression
methods were used for survival analysis.
Results: Preoperative obstructive pneumonitis/atelectasis indicated shorter OS (HR: 1.308; 95% CI:
1.0581.619) and RFS (HR: 1.276; 95% CI: 1.0321.579) as an independent factor. In comparison with
tumor size, we found patients with obstructive pneumonitis/atelectasis and T1 size tumor had similar
prognosis to those with T2 size but without obstructive pneumonitis/atelectasis, and OS, RFS of patients
with obstructive pneumonitis/atelectasis and T2 size were significantly shorter than those with T2 tumor
size but without obstructive pneumonitis/atelectasis, while similar to patients with T3 tumor size but without
obstructive pneumonitis/atelectasis according to division by the eighth edition. We also found obstructive
pneumonitis/atelectasis was significantly related to higher neutrophil (P<0.001), platelet (P<0.001), monocyte
(P<0.001), NLR (P<0.001), PLR (P=0.002), ESR (P<0.001) and lower LMR (P<0.001).
Conclusions: Preoperative obstructive pneumonitis/atelectasis predicted poor survival independently in
non-small cell lung cancer (NSCLC). And we suggested which T staging group the patients with obstructive
pneumonitis/atelectasis would be divided to should depend on tumor size in the eighth TNM staging system.

Keywords: Non-small cell lung cancer (NSCLC); obstructive pneumonitis/atelectasis; tumor size; prognosis

Submitted Nov 21, 2016. Accepted for publication Jan 24, 2017.
doi: 10.21037/jtd.2017.02.88
View this article at: http://dx.doi.org/10.21037/jtd.2017.02.88

Journal of Thoracic Disease. All rights reserved. jtd.amegroups.com J Thorac Dis 2017;9(3):768-778
Journal of Thoracic Disease, Vol 9, No 3 March 2017 769

Introduction 3 and 5 cm in the eighth edition. In order to search predictive

effects of preoperative obstructive pneumonitis/atelectasis and
Lung cancer is the first leading cause among cancer-related
the relationship between obstructive pneumonitis/atelectasis
death worldwide (1). Surgery is a curative strategy, but
and tumor size, we conducted a retrospective for lung cancer
most lung cancer patients lose opportunity of operation
patients receiving surgery in Shandong Provincial Hospital
because lung cancer is hard to be discovered at early stage.
affiliated to Shandong University.
And as cancer cells can easily transfer to blood and lymph
nodes causing metastasis, the prognosis for lung cancer
is unsatisfied yet, with five-year survival rates 18.2% for Methods
non-small cell lung cancer (NSCLC) (2).
Setting and patient selection
Obstructive pneumonitis and atelectasis are common
complications for lung cancer patients before treatment, and We performed a retrospective study about patients
most are discovered while initial diagnosis. They formed due who were diagnosed with lung cancer and received
to the blockage of tracheal bronchus by cancer tissue partially surgical treatment between 2006 and 2011 in Shandong
or completely, which will easily cause repeated infection Provincial Hospital. Patients would be included if they
of the same position or lung tissue shrink. In recent years, met the following criteria: (I) diagnosed with NSCLC
many studies have proved that systemic inflammation and pathologically; (II) receiving tumor resection; (III)
immunology played important roles in development and having Computed tomography reports, X-ray reports of
progression of various cancers. Inflammatory cells interacted chest, bronchofiberscope test results or other evidence
with cell matrix to make up tumor microenvironment, which to classify patients into different groups (presence of
could influence the occurrence and development of neoplasm obstructive pneumonitis/atelectasis or not); (IV) having
(3,4). Several hematological markers, which could reflect the complete serum indicators about inflammation except
status of host inflammation, immunity, and hemostasis, have ESR (erythrocyte sedimentation rate) before surgery; (V)
been reported to have prognostic utility in many cancers (5), having complete follow-up data; (VI) not accompanied with
such as C-reactive protein (CRP), neutrophils, platelets, other cancers. Patients who were undergoing non-cancer
lymphocytes, Glasgow prognostic score, prognostic nutrition related inflammation or did not meet the criteria would be
index (PNI), neutrophil to lymphocyte ratio (NLR), platelet excluded.
to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio
(LMR) (6-12). So we assumed that presence of obstructive
Clinical and follow-up data collection
pneumonitis or atelectasis might be associated with these
inflammation indicators and predicted poor survival. We collected following clinical characteristics about patients:
TNM staging system for lung cancer plays a critical role age, gender, pathological TNM stage, histology, tumor
in determining disease degree, making clinical decisions location, tumor size, tumor differentiation degree, presence
or predicting prognosis (13). T category, which is mainly of obstructive pneumonitis/atelectasis, neutrophil count,
divided by tumor size, is also related to some other non- lymphocyte count, platelet count, monocyte count, ESR,
size-based factors including obstructive pneumonitis or overall survival (OS), recurrence-free survival (RFS). And
atelectasis. In September 2015, the eighth TNM staging we calculated the ratio values such as NLR, PLR, LMR.
system proposal was published. There were some changes Computed tomography reports and bronchofiberscope test
comparing with the seventh edition that was applied in results before surgery were used to confirm the diagnosis of
2009. One was that lung cancer patients associated with obstructive pneumonitis/atelectasis.
atelectasis or obstructive pneumonitis which extended to the OS referred to the time from date of surgery to death for
hilar region either partly or completely were included in T2 any cause. If the patient was alive or out of touch, the endpoint
category (14). Another was about the division of T category of OS was the date of last follow-up. RFS was calculated from
by tumor size, which became more detailed. This change the date of surgery to recurrence. If there was no recurrence,
emphasized the importance of tumor size for prognosis. We the endpoint was the date of death or last follow-up.
found that the division of T2 and T3 became 5 cm instead of
7 cm in the eighth TNM staging proposal. In other words,
Statistical analysis
the prognostic value of obstructive pneumonitis/atelectasis
before surgery should be similar to tumor size between There were both numerical and categorical variables in

Journal of Thoracic Disease. All rights reserved. jtd.amegroups.com J Thorac Dis 2017;9(3):768-778
770 Pang et al. Effect of obstructive pneumonitis/atelectasis

A 1.0 OS P<0.001 1-obstructive pneumonitis/atelectasis

0-no obstructive pneumonitis/atelectasis
B 1.0 RFS P<0.001 1-obstructive pneumonitis/atelectasis
0-obstructive pneumonitis/atelectasis
1-censored 1-censored
0-censored
Cumulative survival
0-censored

Cumulative survival
0.8 0.8

0.6 0.6

0.4 0.4

0.2 0.2

0.0 0.0
0 20 40 60 80 100 120 0 20 40 60 80 100 120

Figure 1 Kaplan-Meier survival curves for overall survival (OS) and recurrence-free survival (RFS) between groups of having and not having
obstructive pneumonitis/atelectasis patients.

description of clinicopathological characteristics. For all patients. Six hundred and twenty nine patients were
further analysis, we changed the former into dichotomous diagnosed of lung adenocarcinoma, while 470 patients were
variables. And the cut-off value was determined by receiver considered as lung squamous cancer. As for TNM stage
operating characteristic (ROC) curve. To search the according to the 7th edition, there were 838 patients at I/II
correlation between obstructive pneumonitis/atelectasis and stage, and others were at III stage.
other clinicopathological variables, we used chi-square test.
When conducting survival analysis, we performed Kaplan-
Survival analysis of obstructive pneumonitis/atelectasis
Meier (K-M) analysis to test if presence of obstructive
pneumonitis/atelectasis before surgery was significant for The K-M curves (Figure 1) showed that there was significant
prognosis, and univariate and multivariate cox regression difference between the two groups (having obstructive
methods were also used to explore significant markers for pneumonitis/atelectasis or not) for OS (P<0.001) and RFS
survival. All statistical calculations were performed by SPSS (P<0.001). And as seen in Table 1, presence of obstructive
(version 20.0) software (Inc., Chicago, IL, USA), and a pneumonitis/atelectasis before surgery suggested poor OS
two-sided P0.05 was considered to be significant. (HR: 1.308; 95% CI: 1.0581.619) and RFS (HR: 1.276;
95% CI: 1.0321.579) as an independent factor.
Results of subgroup analysis were listed in Table 2.
Ethic statement NSCLC patients were stratified into various groups by age,
The study was approved by Ethics Committee of Shandong gender, stage, histological subtype and differential degree.
Provincial Hospital in China (No. 356). Results showed that presence of obstructive pneumonitis/
atelectasis was associated with poorer prognosis significantly
for patients in younger group (OS: HR =1.361, 95%
Results CI: 1.0451.772, P=0.022; RFS: HR =1.310, 95% CI:
Characteristics of patients 1.0041.708, P=0.047), female group (OS: HR =1.651,
95% CI: 1.0582.576, P=0.027; RFS: HR =1.656, 95% CI:
After screening, 1,177 NSCLC patients containing 1.0652.573, P=0.025), I/II stage group (OS: HR =1.520,
342 (29.1%) females and 835 (70.9%) males were included 95% CI: 1.1272.049, P=0.006; RFS: HR =1.438, 95% CI:
in our study finally. The mean age of those patients was 1.0661.939, P=0.017), adenocarcinoma group (OS: HR
58.5 ranging from 20 to 83, and there were 859 (73.0%) =1.458, 95% CI: 1.0612.003, P=0.020; RFS: HR =1.431,
patients 65 years old and 318 (27.0%) patients >65 years 95% CI: 1.0411.967, P=0.027), well (OS: HR =4.719,
old. Four hundred and twenty (35.7%) patients were 95% CI: 1.11320.010, P=0.035; RFS: HR =4.750, 95%
diagnosed for accompanying with obstructive pneumonitis/ CI: 1.19118.949, P=0.027), moderately differential degree
atelectasis. The incidence of this complication might differ groups (OS: HR =1.337, 95% CI: 1.0001.788, P=0.04;
from region to region. There were 209 (17.8%) patients RFS: HR =1.338, 95% CI: 1.0021.788, P=0.049) and
out of touch during our follow-up, and the mean survival N0 stage group (OS: HR =1.511, 95% CI: 1.0262.2248,
were 44.4 months for OS and 39.1 months for RFS of P=0.037; RFS: HR =1.630, 95% CI: 1.1552.300, P=0.005).

Journal of Thoracic Disease. All rights reserved. jtd.amegroups.com J Thorac Dis 2017;9(3):768-778
 Table 1 Univariate and multivariate analysis of prognostic factors for OS and RFS

OS RFS

Characteristics Univariate Multivariate Univariate Multivariate

HR (95% CI) P HR (95% CI) P HR (95% CI) P HR (95% CI) P

Age

ge Reference Reference Reference Reference

>65 1.477 (1.2071.807) <0.001 1.823 (1.4802.245) <0.001 1.477 (1.2071.807) <0.001 1.802 (1.4642.219) <0.001

Gender

Female Reference Reference Reference Reference

Male 1.410 (1.1271.763) 0.003 1.063 (0.7821.443) 0.697 1.407 (1.1251.760) 0.003 1.047 (0.7731.420) 0.766

Journal of Thoracic Disease. All rights reserved.

Histological subtype

Adenocarcinoma Reference Reference Reference Reference

Journal of Thoracic Disease, Vol 9, No 3 March 2017

Squamous carcinoma 1.277 (1.0471.558) 0.016 0.900 (0.7041.136) 0.359 1.280 (1.0491.561) 0.015 0.885 (0.6971.124) 0.316

Others 1.252 (0.8581.827) 0.243 1.699 (1.0372.783) 0.035 1.285 (0.8811.875) 0.193 1.843 (1.1133.053) 0.018

Smoking index

100 Reference Reference Reference Reference

>100 1.513 (1.2321.859) <0.001 1.192 (0.8951.601) 0.225 1.524 (1.2411.873) <0.001 1.207 (0.9051.609) 0.200

Obstructive pneumonitis/atelectasis

jtd.amegroups.com
No Reference Reference Reference Reference

Yes 1.605 (1.3241.946) <0.001 1.308 (1.0581.619) 0.013 1.560 (1.2871.890) <0.001 1.276 (1.0321.579) 0.025

Pathological TNM stage

I/II Reference Reference Reference Reference

III 3.152 (2.6003.821) <0.001 3.115 (2.5463.811) <0.001 3.032 (2.5023.675) <0.001 2.975 (2.4343.637) <0.001

Differentiation degree

Well Reference Reference Reference Reference

Moderate 3.280 (2.0555.236) <0.001 2.397 (1.4813.879) <0.001 3.533 (2.2135.639) <0.001 2.625 (1.6224.248) <0.001

Poor 3.807 (2.3586.145) <0.001 2.503 (1.5324.089) <0.001 3.991 (2.4726.443) <0.001 2.655 (1.6254.340) <0.001

P0.05 was considered to be significant. OS, overall survival; RFS, recurrence-free survival; HR, hazard ratio; CI, confidence interval.

J Thorac Dis 2017;9(3):768-778

771
 Table 2 Subgroup analysis of prognostic effect of obstructive pneumonitis/atelectasis for OS and RFS
772
OS RFS
Number of
Characteristics Univariate Multivariate Univariate Multivariate
patients
HR (95% CI) P HR (95% CI) P HR (95% CI) P HR (95% CI) P

Age

ge 859 1.786 (1.4122.258) <0.001 1.361 (1.0451.772) 0.022 1.733 (1.3702.191) <0.001 1.310 (1.0041.708) 0.047

>65 318 1.376 (0.9771.938) 0.068 1.184 (0.8131.725) 0.379 1.351 (0.9601.903) 0.085 1.196 (0.8231.737) 0.348

Gender

Female 342 1.924 (1.2692.917) 0.002 1.651 (1.0582.576) 0.027 1.951 (1.2872.958) 0.002 1.656 (1.0652.573) 0.025

Male 835 1.450 (1.1641.805) 0.001 1.219 (0.9561.555) 0.110 1.393 (1.1991.734) 0.003 1.176 (0.9221.500) 0.191

Journal of Thoracic Disease. All rights reserved.

Stage

I/II 838 1.560 (1.1892.046) 0.001 1.520 (1.1272.049) 0.006 1.513 (1.1541.985) 0.003 1.438 (1.0661.939) 0.017

III 339 1.196 (0.9081.575) 0.203 1.150 (0.8491.559) 0.367 1.175 (0.8921.548) 0.251 1.171 (0.8641.588) 0.309

Histological subtype

Squamous carcinoma 470 1.379 (1.0231.858) 0.035 1.233 (0.9081.675) 0.180 1.311 (0.9731.767) 0.076 1.194 (0.8791.623) 0.256

Adenocarcinoma 629 1.991 (1.4612.713) <0.001 1.458 (1.0612.003) 0.020 1.972 (1.4482.688) <0.001 1.431 (1.0411.967) 0.027

Differentiation degree

Well 147 3.671 (1.30610.318) 0.014 4.719 (1.11320.010) 0.035 3.697 (1.31510.389) 0.013 4.750 (1.19118.949) 0.027

jtd.amegroups.com
Moderate 595 1.509 (1.1681.950) 0.002 1.337 (1.0001.788) 0.04 1.455 (1.1271.880) 0.004 1.338 (1.0021.788) 0.049

Poor 341 1.290 (0.9251.798) 0.134 1.254 (0.8781.791) 0.213 1.216 (0.8721.695) 0.249 1.164 (0.8151.664) 0.403

N stage

N0 656 1.631 (1.1552.302) 0.005 1.511 (1.0262.224) 0.037 1.486 (1.0092.187) 0.045 1.630 (1.1552.300) 0.005

N1 244 0.913 (0.6291.326) 0.633 0.953 (0.6241.457) 0.825 0.805 (0.5551.168) 0.253 0.825 (0.5371.268) 0.381

N2 266 1.414 (1.0401.922) 0.027 1.306 (0.9331.829) 0.120 1.443 (1.0611.962) 0.019 1.426 (1.0211.991) 0.038

P0.05 was considered to be significant. OS, overall survival; RFS, recurrence-free survival; HR, hazard ratio; CI, confidence interval.

J Thorac Dis 2017;9(3):768-778

Pang et al. Effect of obstructive pneumonitis/atelectasis
Journal of Thoracic Disease, Vol 9, No 3 March 2017 773

A 1.0 OS (1) tumor size 3 cm with obstructive

pneumonitis/atelectasis B 1.0 RFS (1) tumor size <3 cm with obstructive
pneumonitis/atelectasis
(2) tumor size 3 cm without obstructive (2) tumor size <3 cm without obstructive
pneumonitis/atelectasis pneumonitis/atelectasis

Cumulative survival
Cumulative survival

0.8 (3) 3< tumor size 7 cm without obstructive

pneumonitis/atelectasis
0.8 (3) 3< tumor size <7 cm without obstructive
pneumonitis/atelectasis
(1)-censored (1)-censored
(2)-censored (2)-censored
0.6 (3)-censored 0.6 (3)-censored

0.4 0.4

0.2 0.2
(1) vs. (2): P<0.001 (1) vs. (2): P<0.001
0.0 (1) vs. (3): P=0.709 0.0 (1) vs. (3): P=0.726
0 20 40 60 80 100 120 0 20 40 60 80 100 120

C 1.0 OS (1) 3< tumor size <7 cm with obstructive

pneumonitis/atelectasis D 1.0 RFS (1) 3< tumor size 7 cm with obstructive
pneumonitis/atelectasis
(2) tumor size 3 cm without obstructive (2) tumor size 3 cm without obstructive
pneumonitis/atelectasis pneumonitis/atelectasis

Cumulative survival
(3) 3< tumor size 7 cm without obstructive (3) 3< tumor size 7 cm without obstructive
Cumulative survival

0.8 pneumonitis/atelectasis 0.8 pneumonitis/atelectasis

(1)-censored (1)-censored
(2)-censored (2)-censored
0.6 (3)-censored 0.6 (3)-censored

0.4 0.4

0.2 0.2
(1) vs. (2): P<0.001 (1) vs. (2): P<0.001
0.0 (1) vs. (3): P=0.194 0.0 (1) vs. (3): P=0.347
0 20 40 60 80 100 120 0 20 40 60 80 100 120

Figure 2 Kaplan-Meier survival curves of obstructive pneumonitis/atelectasis and tumor size according to the seventh TNM staging system
for overall survival (OS) and recurrence-free survival (RFS). (A,B) OS and RFS curves for patients in T1O7, T1NO7 and T2NO7 groups;
(C,D) OS and RFS curves for patients in T2O7, T1NO7 and T2NO7 groups.

Univariate and multivariate analysis of prognostic factors obstructive pneumonitis/atelectasis, T1NO7); (IV) patients
without preoperative obstructive pneumonitis/atelectasis
Firstly, we used univariate analysis to search significant
and tumor size between 3 and 7 cm (T2 tumor size in
factors for OS and RFS. Then age, gender, histological
7 th edition without obstructive pneumonitis/atelectasis,
subtype, smoking index, presence of obstructive
T2NO7). Figure 2 showed K-M curves of T1O7 and T2O7
pneumonitis/atelectasis, pathological TNM stage and
groups comparing with the other two groups for OS and
differential degree met the criteria to be included in
RFS respectively, and there was no statistically significant
multivariate analysis. As presented in Table 1, age, presence difference between T1O7 group and T2NO7 group for
of obstructive pneumonitis/atelectasis, pathological OS and RFS (OS: P=0.709; RFS: P=0.726). The result was
TNM stage and differential degree were confirmed to be same for T2O7 group and T2NO7 group (OS: P=0.194;
independent prognostic indicators for NSCLC patients. RFS: P=0.347). The curves also revealed that patients in
T1O7 group had negative prognosis comparing with those
Comparison about prognostic effects between obstructive in T1NO7 group (OS: P<0.001; RFS: P<0.001).
pneumonitis/atelectasis and tumor size And according to the eighth edition, we selected five
groups of patients: (I) patients with preoperative obstructive
According to the seventh edition of TNM staging system, pneumonitis/atelectasis and tumor size 3 cm (T1 size in
we selected four groups of patients: (I) patients with 8th edition with obstructive pneumonitis/atelectasis, T1O8);
preoperative obstructive pneumonitis/atelectasis and tumor (II) patients having obstructive pneumonitis/atelectasis and
size 3 cm (T1 tumor size in 7th edition with obstructive tumor size between 3 and 5 cm before surgery (T2 size in
pneumonitis/atelectasis, T1O7); (II) patients having 8th edition with obstructive pneumonitis/atelectasis, T2O8);
obstructive pneumonitis/atelectasis and tumor size between (III) patients without preoperative obstructive pneumonitis/
3 and 7 cm before surgery (T2 tumor size in 7th edition with atelectasis and tumor size 3 cm (T1 size in 8th edition
obstructive pneumonitis/atelectasis, T2O7); (III) patients without obstructive pneumonitis/atelectasis, T1NO8); (IV)
without preoperative obstructive pneumonitis/atelectasis patients without preoperative obstructive pneumonitis/
and tumor size 3 cm (T1 tumor size in 7th edition without atelectasis and tumor size between 3 and 5 cm (T2 size in

Journal of Thoracic Disease. All rights reserved. jtd.amegroups.com J Thorac Dis 2017;9(3):768-778
774 Pang et al. Effect of obstructive pneumonitis/atelectasis

A 1.0 OS (1) tumor size 3 cm with obstructive

pneumonitis/atelectasis B 1.0 RFS (1) tumor size 3 cm with obstructive
pneumonitis/atelectasis
(2) tumor size 3 cm without obstructive (2) tumor size 3 cm without obstructive
pneumonitis/atelectasis pneumonitis/atelectasis
Cumulative survival

Cumulative survival
0.8 (3) 3< tumor size 5 cm without obstructive 0.8 (3) 3< tumor size 5 cm without obstructive
pneumonitis/atelectasis pneumonitis/atelectasis
(4) 5< tumor size 7 cm without obstructive (4) 5< tumor size 7 cm without obstructive
0.6 pneumonitis/atelectasis 0.6 pneumonitis/atelectasis
(1)-censored (1)-censored
(2)-censored (2)-censored
0.4 (3)-censored (3)-censored
0.4
(4)-censored (4)-censored

0.2 0.2
(1) vs. (2): P<0.001 (1) vs. (2): P<0.001
(1) vs. (3): P=0.931 (1) vs. (3): P=0.910
0.0 (1) vs. (4): P=0.136 0.0 (1) vs. (4): P=0.118
0 20 40 60 80 100 120 0 20 40 60 80 100 120

C 1.0 OS (1) 3< tumor size 5 cm with obstructive

pneumonitis/atelectasis D 1.0 RFS (1) 3< tumor size 5 cm with obstructive
pneumonitis/atelectasis
(2) tumor size 3 cm without obstructive (2) tumor size 3 cm without obstructive
pneumonitis/atelectasis pneumonitis/atelectasis
Cumulative survival

Cumulative survival
0.8 (3) 3< tumor size 5 cm without obstructive 0.8 (3) 3< tumor size 5 cm without obstructive
pneumonitis/atelectasis pneumonitis/atelectasis
(4) 5< tumor size 7 cm without obstructive (4) 5< tumor size 7 cm without obstructive
0.6 pneumonitis/atelectasis 0.6 pneumonitis/atelectasis
(1)-censored (1)-censored
(2)-censored (2)-censored
0.4 (3)-censored 0.4 (3)-censored
(4)-censored (4)-censored

0.2 0.2
(1) vs. (2): P<0.001 (1) vs. (2): P<0.001
(1) vs. (3): P=0.033 (1) vs. (3): P=0.075
0.0 (1) vs. (4): P=0.786 0.0 (1) vs. (4): P=0.613
0 20 40 60 80 100 120 0 20 40 60 80 100 120

Figure 3 Kaplan-Meier survival curves of obstructive pneumonitis/atelectasis and tumor size according to the eighth TNM staging system
for overall survival (OS) and recurrence-free survival (RFS). (A,B) OS and RFS curves for patients in T1O8, T1NO8, T2NO8 and T3NO8
groups; (C,D) OS and RFS curves for patients in T2O8, T1NO8, T2NO8 and T3NO8 groups.

8 th edition without obstructive pneumonitis/atelectasis, difference of lymphocyte number between having and not
T2NO8); (V) patients without preoperative obstructive having obstructive pneumonitis/atelectasis groups was not
pneumonitis/atelectasis and tumor size between 5 and 7 cm significant (P=0.469).
(T3 size in 8th edition without obstructive pneumonitis/
atelectasis, T3NO8). Figure 3 showed K-M curves of T1O8
Discussion
and T2O8 groups comparing with the other three groups
for OS and RFS respectively, and there was no statistically The TNM staging system was first established in 1973 by
significant difference about prognosis of patients in T1O8 The American Joint Committee on Cancer (AJCC) and the
group and those in T2NO8 and T3NO8 groups (for the Union Internationale Contre le Cancer (13). In September
T2NO8 group OS: P=0.931; RFS: P=0.910; for T3NO8 2015, the proposal of the eighth version was published.
group OS: P=0.136; RFS: P=0.118). But for patients in There were some slight changes comparing to the seventh
T2O8 group, their OS was significantly shorter than those edition which was applied in 2009, but presence of
in T2NO8 group (P=0.033), but similar with patients in obstructive pneumonitis/atelectasis is still one of the non-
T3NO8 group (P=0.786). size based descriptors for T category. Ou et al.s study once
confirmed that visceral pleura invasion, hilar atelectasis, or
obstructive pneumonitis with tumor size >3 cm were poor
Factors associated with obstructive pneumonitis/atelectasis
prognostic factors for survival, but they predicted favorable
The cut-off values of each inflammation maker by ROC prognosis when tumor size 3 cm (15). Besides, Dediu and
curves were as follows: neutrophil 4.5; lymphocyte 1.5; Bulbul et al.s articles showed the positive prognostic value
platelet 189.5; monocyte 0.5; NLR 2.475; PLR 169.8; of obstructive pneumonitis/atelectasis in patients with
LMR 3.685; ESR 10.5. Table 3 showed that presence advanced lung cancer (16,17). They thought the favorable
of obstructive pneumonitis/atelectasis was significantly effect of atelectasis might owe to the decreased intratumoral
related to higher neutrophil (P<0.001), platelet (P=0.012), blood flow and a specific growth pattern.
monocyte (P<0.001), NLR (P<0.001), PLR (P=0.002), In order to figure out the controversial issue, we
ESR (P<0.001) and lower LMR (P<0.001). But the conducted a retrospective study based on 1,177 NSCLC

Journal of Thoracic Disease. All rights reserved. jtd.amegroups.com J Thorac Dis 2017;9(3):768-778
Journal of Thoracic Disease, Vol 9, No 3 March 2017 775

Table 3 Clinicopathological and inflammation factors associated with obstructive pneumonitis/atelectasis

Factors Number of patients No obstructive pneumonitis/atelectasis (%) Obstructive pneumonitis/atelectasis (%) P
Age 0.047
65 859 538 (62.6) 321 (37.4)
>65 318 219 (68.9) 99 (31.1)
Gender <0.001
Female 342 267 (78.1) 75 (21.9)
Male 835 490 (58.7) 345 (41.3)
Histological subtype <0.001
Adenocarcinoma 629 515 (81.9) 114 (18.1)
Squamous carcinoma 470 198 (42.1) 272 (57.9)
Others 78 44 (56.4) 34 (43.6)
Pathological TNM stage <0.001
I/II 838 576 (68.7) 262 (31.3)
III 339 181 (53.4) 158 (46.6)
Neutrophil <0.001
4.5 749 525 (70.1) 224 (29.9)
>4.5 428 232 (54.2) 196 (45.8)
Lymphocyte 0.469
>1.5 839 545 (65.0) 294 (35.0)
1.5 338 212 (62.7) 126 (37.3)
Platelet 0.012
189.5 282 199 (70.6) 83 (29.4)
>189.5 895 558 (62.3) 337 (70.6)
Monocyte <0.001
0.5 702 502 (71.5) 200 (28.5)
>0.5 475 255 (53.7) 220 (46.3)
NLR <0.001
2.475 713 489 (68.6) 224 (31.4)
>2.475 464 268 (57.8) 196 (42.4)
PLR 0.002
169.8 914 609 (66.6) 305 (33.4)
>169.8 263 148 (56.3) 115 (43.7)
LMR <0.001
>3.685 644 463 (71.9) 181 (29.1)
3.685 533 294 (55.2) 239 (44.8)
ESR <0.001
10.5 162 123 (75.9) 39 (24.1)
>10.5 280 147 (52.5) 133 (47.5)
SCLC, small cell lung cancer; NLR, neutrophil to lymphocyte ratio; PLR, platelet to lymphocyte ratio; LMR, lymphocyte to monocyte ratio;
ESR, erythrocyte sedimentation rate. P0.05 was considered to be significant.

Journal of Thoracic Disease. All rights reserved. jtd.amegroups.com J Thorac Dis 2017;9(3):768-778
776 Pang et al. Effect of obstructive pneumonitis/atelectasis

patients receiving surgery treatment in Shandong Provincial We found that presence of obstructive pneumonitis/
Hospital affiliated to Shandong University between 2006 atelectasis was significantly relative to higher neutrophil,
and 2011. However, our study suggested that presence of platelet, monocyte, NLR, PLR, ESR and lower LMR. The
obstructive pneumonitis/atelectasis before surgery predicted biological reason behind prognostic effect of preoperative
shorter OS and RFS as an independent factor. In subgroup obstructive pneumonitis/atelectasis might owe to high
analysis, we found there was no significant difference level of neutrophil, platelet and monocyte. Some studies
between having preoperative obstructive pneumonitis/ have suggested that a large amount of neutrophils might
atelectasis or not for prognosis of patients in stage III, while have negative effect on tumor growth by influencing
survival differed significantly for patients in I/II stage. As to cytolytic activity of lymphocyte or natural killer cells and
patients with cancer cells differentiating well or moderately, inhibit proliferation of T-cells (20). Elevated platelet count
a significant result was also observed. was also confirmed to be a negative factor for prognosis
Whats more, we searched the relationship between of lung cancer patients due to releasing some platelet-
obstructive pneumonitis/atelectasis and tumor size for derived cytokines related to tumor angiogenesis regulatory,
survival. In the eighth TNM staging proposal for lung such as vascular endothelial growth factor (VEGF), basic
cancer, the tumor size to divide T2 and T3 became 5 cm, fibroblast growth factor (bFGF), platelet derived growth
not 7 cm comparing with the seventh edition. And lung factor (PDGF) (21). Evidence also showed that tumor-
cancer patients with obstructive pneumonitis/atelectasis related macrophages which derived from circulating
partially or completely are included in T2 category. monocytes were related to poor survival in various
It seemed that they thought the prognostic value of cancers. Macrophages could secrete TNF-, VEGF,
obstructive pneumonitis/atelectasis before surgery was epidermal growth factor, promoting tumor angiogenesis
similar to the factor of tumor size between 3 and 5 cm in and tumor growth (22-24). However, underlying infection
the eighth edition. In order to find out the problem, we within the obstructed space might also contribute to the
divided the patients into different groups according to result. Although we have excluded the patients who were
the seventh and the eighth edition respectively, which was undergoing non-cancer related inflammation, some bias
mentioned in the part of results. According to the division might exist, so further researches should be conducted.
by the seventh edition, K-M curves (Figure 2) indicated In conclusion, presence of obstructive pneumonitis/
that there were no significant differences comparing T1O7 atelectasis before surgery in lung cancer patients predicted
group, T2O7 group with T2NO7 group. When divided poor OS and RFS independently. This was particularly
according to the eighth edition, the prognosis of patients obvious for patients in early stage group, younger group,
in T1O8 group was similar to those in T2NO8 group, but female group, adenocarcinoma group and group of tumor
the survival of patients in T2O8 group were significantly cells differentiating well or moderately. There was no
shorter than those in T2NO8 group, while similar with significant difference for patients in advanced stage. And in
patients in T3NO8 group. So we suggested that which T comparison the predictive effects of preoperative obstructive
staging group the patients with obstructive pneumonitis/ pneumonitis/atelectasis with tumor size, we found that
atelectasis should be divided to should depend on the tumor the prognosis of patients with obstructive pneumonitis/
size in the eighth TNM staging system. atelectasis and T1 tumor size was similar to patients with
However, the mechanism of preoperative obstructive T2 tumor size but without obstructive pneumonitis/
pneumonitis/atelectasiss negative effect on survival was not atelectasis, while the survival of patients with obstructive
sure yet. Miyamoto et al.s study on clinical investigation pneumonitis/atelectasis and T2 tumor size was significantly
of obstructive pneumonia with lung cancer indicated that shorter than patients with T2 tumor size but without
the majority had neutrophilia and high CRP (18). An obstructive pneumonitis/atelectasis, and similar to patients
authoritative study once mentioned inflammation was a with T3 tumor size but without obstructive pneumonitis/
critical hallmark of cancer, which could affect occurrence atelectasis according to division by the eighth edition.
and development of neoplasm (19). And recently, some Our results also showed that presence of preoperative
inflammation makers included neutrophil, CRP, lymphocyte obstructive pneumonitis/atelectasis was associated with
and other specific values were reported to be associated higher neutrophil, platelet, monocyte, NLR, PLR, ESR and
with prognosis of lung cancer patients. So a research to lower LMR, which might play a role in its negative effect
search the relationship between them was conducted. for survival.

Journal of Thoracic Disease. All rights reserved. jtd.amegroups.com J Thorac Dis 2017;9(3):768-778
Journal of Thoracic Disease, Vol 9, No 3 March 2017 777

Acknowledgements 10. Mori S, Usami N, Fukumoto K, et al. The Significance

of the Prognostic Nutritional Index in Patients with
F und in g : Th is w o rk w a s s u p p o rted b y Pro vin cial
Completely Resected Non-Small Cell Lung Cancer. PLoS
science and technology development plan of Shandong
One 2015;10:e0136897.
(2015GSF118063), Shandong Provincial Natural Science
11. Shrotriya S, Walsh D, Bennani-Baiti N, et al. C-Reactive
foundation (ZR2014HQ028, ZR2014HQ073).
Protein Is an Important Biomarker for Prognosis
Tumor Recurrence and Treatment Response in Adult
Footnote Solid Tumors: A Systematic Review. PLoS One
2015;10:e0143080.
Conflicts of Interest: The authors have no conflicts of interest
12. Templeton AJ, Ace O, McNamara MG, et al. Prognostic
to declare.
role of platelet to lymphocyte ratio in solid tumors: a
systematic review and meta-analysis. Cancer Epidemiol
Ethical Statement: The study was approved by Ethics
Biomarkers Prev 2014;23:1204-12.
Committee of Shandong Provincial Hospital in China
13. Mountain CF, Carr DT, Anderson WA. A system for the
(No. 356).
clinical staging of lung cancer. Am J Roentgenol Radium
Ther Nucl Med 1974;120:130-8.
References 14. Goldstraw P, Chansky K, Crowley J, et al. The IASLC
1. Jemal A, Bray F, Center MM, et al. Global cancer statistics. Lung Cancer Staging Project: Proposals for Revision of
CA Cancer J Clin 2011;61:69-90. the TNM Stage Groupings in the Forthcoming (Eighth)
2. DeSantis CE, Lin CC, Mariotto AB, et al. Cancer Edition of the TNM Classification for Lung Cancer. J
treatment and survivorship statistics, 2014. CA Cancer J Thorac Oncol 2016;11:39-51.
Clin 2014;64:252-71. 15. Ou SH, Zell JA, Ziogas A, et al. Prognostic significance of
3. Candido J, Hagemann T. Cancer-related inflammation. J the non-size-based AJCC T2 descriptors: visceral pleura
Clin Immunol 2013;33 Suppl 1:S79-84. invasion, hilar atelectasis, or obstructive pneumonitis in
4. Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: stage IB non-small cell lung cancer is dependent on tumor
integrating immunity's roles in cancer suppression and size. Chest 2008;133:662-9.
promotion. Science 2011;331:1565-70. 16. Bulbul Y, Eris B, Orem A, et al. Pulmonary atelectasis and
5. Crusz SM, Balkwill FR. Inflammation and cancer: advances survival in advanced non-small cell lung carcinoma. Ups J
and new agents. Nat Rev Clin Oncol 2015;12:584-96. Med Sci 2010;115:176-80.
6. Tomita M, Shimizu T, Hara M, et al. Preoperative 17. Dediu M, Crisan E, Radut M, et al. The favorable
leukocytosis, anemia and thrombocytosis are associated prognostic significance of atelectasis in patients with
with poor survival in non-small cell lung cancer. advanced non-small cell lung cancer: results of a prospective
Anticancer Res 2009;29:2687-90. observational study. Lung Cancer 2009;63:271-6.
7. Laird BJ, Kaasa S, McMillan DC, et al. Prognostic 18. Miyamoto J, Koga H, Kohno S, et al. Clinical
factors in patients with advanced cancer: a comparison investigation of obstructive pneumonia with lung cancer.
of clinicopathological factors and the development of an Kansenshogaku Zasshi 1994;68:728-33.
inflammation-based prognostic system. Clin Cancer Res 19. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell
2013;19:5456-64. 2000;100:57-70.
8. Cedrs S, Torrejon D, Martnez A, et al. Neutrophil to 20. Pillay J, Kamp VM, van Hoffen E, et al. A subset of
lymphocyte ratio (NLR) as an indicator of poor prognosis neutrophils in human systemic inflammation inhibits T cell
in stage IV non-small cell lung cancer. Clin Transl Oncol responses through Mac-1. J Clin Invest 2012;122:327-36.
2012;14:864-9. 21. Peterson JE, Zurakowski D, Italiano JE Jr, et al. VEGF,
9. Proctor MJ, Morrison DS, Talwar D, et al. A comparison PF4 and PDGF are elevated in platelets of colorectal
of inflammation-based prognostic scores in patients with cancer patients. Angiogenesis 2012;15:265-73.
cancer. A Glasgow Inflammation Outcome Study. Eur J 22. Leek RD, Harris AL. Tumor-associated macrophages
Cancer 2011;47:2633-41. in breast cancer. J Mammary Gland Biol Neoplasia

Journal of Thoracic Disease. All rights reserved. jtd.amegroups.com J Thorac Dis 2017;9(3):768-778
778 Pang et al. Effect of obstructive pneumonitis/atelectasis

2002;7:177-89. 24. Xiong M, Elson G, Legarda D, et al. Production of

23. Mantovani A, Schioppa T, Porta C, et al. Role of tumor- vascular endothelial growth factor by murine macrophages:
associated macrophages in tumor progression and invasion. regulation by hypoxia, lactate, and the inducible nitric
Cancer Metastasis Rev 2006;25:315-22. oxide synthase pathway. Am J Pathol 1998;153:587-98.

Cite this article as: Pang Z, Ding N, Dong W, Ni Y, Zhang

T, Qu X, Du J, Liu Q. Prognostic effects of preoperative
obstructive pneumonitis or atelectasis and comparison with
tumor size in non-small cell lung cancer. J Thorac Dis
2017;9(3):768-778. doi: 10.21037/jtd.2017.02.88

Journal of Thoracic Disease. All rights reserved. jtd.amegroups.com J Thorac Dis 2017;9(3):768-778