Introduction
The first-line method of treatment is surgery in cases of
early-stage non-small cell lung cancer (NSCLC) and a
lobectomy is most performed through an open thoracotomy,
while Video-Assisted Thoracic Surgery (VATS)
resections with the developed camera systems and surgical
instruments can be done more rapidly through
shorter incisions and are safe and an applicable alternative,
with a gradually increasing frequency of use.[-]
In addition to the safety of thoracoscopic lobectomy
procedures suggested in many studies in literature, their
various advantages have been demonstrated through
comparisons with the conventional thoracotomy approach,
including shorter hospital stays and chest tube
duration, lower post-operative pain, better preservation
of pulmonary functions, lesser release of cytokines, and
lower rates of general complications.[-] Long-term results
such as general mortality and recurrence were also
demonstrated to be similar or superior in patients who
underwent a VATS lobectomy when compared to those
who underwent an conventional lobectomy.[,]
Disease-free survival and recurrence rates were found
to be similar in the comparison of the VATS lobectomy and
conventional thoracotomy approaches in the ACOSOG
Z0030 (ALLIANCE) study.[] The incidence of development
of a second primary lung cancer has been reported
to be similar after lobectomies performed through a thoracoscopy
and conventional methods in a study by Flores
et al.[] in which it was demonstrated that thoracoscopic
lobectomy was oncologically acceptable.[,-]
A positive effect of adjuvant chemotherapy on survival
has been reported in randomized studies in cases
of NSCLC.[-] Patients who have undergone a
VATS lobectomy and require adjuvant chemotherapy
following pathological staging are expected to be more
compliant to treatment, as post-operative complications
are observed at a lower rate and patients return to
social life more rapidly. There are only a limited number
of studies in the literature addressing this issue, and
so the present study makes a comparison of the adherence
of patients who have undergone thoracoscopic or
conventional lobectomy to adjuvant chemotherapy.
Methods
This research is a retrospective and observational study.
E-46418926-050.01.04--3065. It was carried out in our
clinic following the approval of the ethics committee
on the January 15, 2021.
Patient Selection
A total of 2903 patients diagnosed with NSCLC who
underwent an anatomical lung resection by videothoracoscopic
(n=163) method or by thoracotomy
(n=2740) were analyzed retrospectively between January
2010 and January 2018.
Patients who underwent adjuvant chemotherapy
postoperatively under the Adjuvant Navelbine International
Trialist Association (ANITA) protocol with
Cisplatin 75 mg/m2 and Nevalbine 25 mg/m2 were
included in the study. Patients who received adjuvant
chemotherapy or who completed the adjuvant chemotherapy
protocol at another center, patients who
underwent pre-operative neoadjuvant or adjuvant chemotherapy
and/or radiotherapy, who had a positive
indication of RT for postoperative positive N2 involvement
or chest wall involvement, who had a bilobectomy/
pneumonectomy and extended lung resection, or
who had post-operative complications were excluded
from the study. The starting time of chemotherapy,
doses of chemotherapy, reduced dosages, and delayed
doses were regulated by the medical oncologist.
A total of 84 patients with similar comorbid and
demographic specifications who underwent a lobectomy
by thoracoscopy (n=36) or thoracotomy (n=48)
were included in the study. The age, gender, tumor
localization, dimensions, and N status were similar
in both groups. The age, gender, operated site, type
of operation, tumor type, dimension of tumor, N status,
duration of hospital stay, duration of initiation of
chemotherapy, chemotherapy doses applied, and rate
of completion of the chemotherapy protocol were analyzed
retrospectively.
Staging and Surgical Technique
All patients were evaluated through a thoracic and upper
abdominal computed tomography, a positron emission
tomography, and cranial magnetic resonance imaging.
A cervical mediastinoscopy was performed for mediastinal
lymph node evaluation before lung resections.
All patients in the study underwent a lobectomy and a
mediastinal lymph node dissection; and patients who underwent
a bilobectomy, pneumonectomy, sleeve lobectomy,
or extended resection were excluded from the study.
A conventional thoracotomy was performed
through entry to the thorax through the fifth intercostal
space by a serratus anterior muscle-preserving posterolateral
thoracotomy.
A thoracoscopic lobectomy was performed biportal.
The thoracoscope was placed at the sixth or seventh
intercostal space on the posterior axillary line and a utility thoracotomy was performed at the anterior part
of the fourth intercostal space, 4-7 cm in length. No
retractor was used in any patient.
An intraoperative mediastinal lymph node dissection
was performed on patients who underwent a thoracoscopy
and thoracotomy.
Statistical Analysis
SPSS 26 (IBM Corp, 2019, IBM SPSS Statistics for Windows,
Version 26.0. Armonk, NY) was used to process the
data obtained in the study. The conformity of the data to
the normal distribution was evaluated with histograms,
Q-Q plots, and the Shapiro-Wilk test. Continuous data
conforming to the normal distribution are expressed as
the mean and standard deviation, non-conforming data
are expressed as the median and quartile range of 25-
75%, and nominal variables are expressed as frequency
and percentage. An intergroup comparison t-test was
used for continuous data with normal distribution and
the Mann-Whitney U test was used for data that did not
fit. The Chi-square and, where necessary, Fisher's Exact
tests were used to compare nominal variables.
Results
The results included in the study were 84 patients who
underwent adjuvant chemotherapy following a lobectomy
due to the presence of a NSCLC. Among the patients
undergoing a lobectomy, 36 were through thoracoscopy
and 48 through thoracotomy.
The mean age of the sample was 59.0 (57.3-60.7)
years in the total series, and 58.3 (56.0-60.7) years in the
VATS group and 59.5 (57.1-61.9) years in thoracotomy
group. Gender distribution was as follows: 27 males
and nine females in the VATS group and 38 males and
10 females in the thoracotomy group, corresponding
to 65 males and 19 females in the total series. Among
the operations, 43 were applied on the right and 41 on
the left sides of the patients. The demographics of both
groups were similar (Table 1).
Table 1: Patient demographics
The mean duration of hospital stay was 4.1 days
(3.6-4.7) and 7.3 (6.7-8.2) days in the VATS and thoracotomy
groups, respectively. The duration of hospital
stay was statistically significantly shorter in the VATS
group (p<0.001).
A histopathological evaluation revealed a squamous
cell carcinoma and adenocarcinoma in 29 and 55 patients,
respectively. Of the patients diagnosed with adenocarcinoma,
29 were in the VATS group 26 in the thoracotomy
group, while seven and 22 patients who had a
squamous cell carcinoma were in the VATS and thoracotomy
group, respectively. Considering the distribution
of cancer histopathology, adenocarcinoma cases were
significantly higher in the VATS group (p=0.01); squamous
cell cancer was similar in both groups, there was
statistically significant difference. Survival study between
groups was not performed due to histological difference.
In the VATS group, 26 of the patients received
chemotherapy due to tumor dimension and 10 due to
N1 lymph node involvement, while 34 and 14 patients
in the thoracotomy group received chemotherapy due
to tumor dimension and lymph node involvement, respectively.
The reason of received chemotherapy was
similar in both groups, with no statistically significant
difference (p>0.05).
The duration until the initiation of chemotherapy
was 29.1 (25.7-32.6) days in the VATS group and 36.9
(34.1-39.8) days in the thoracotomy group (p=0.002).
Adjusted to the ANITA protocol, the ratio of application
of the cisplatin dose was 82.9 (81.4-84.5)% in the VATS
group and 77.6 (75.1-80.1)% in the thoracotomy group
(p=0.004), while the ratio of application of the Nevalbine
dose was 82.4 (79.9-84.9)% in the VATS group and 74.8
(71.0-78.6)% in the thoracotomy group (p=0.004) (Table
1). Duration until the initiation of chemotherapy, dose
application ratio of Cisplatin and Nevalbine were statistically
significantly different in two groups.
Discussion
Developments in medicine have led to improvements
in the treatment of disease and decrease in mortality
and morbidity, thus increasing patient comfort and satisfaction.
Advances in minimal invasive surgery over
the past two decades can be evaluated as an indicator
of this approach.
The thoracoscopic lobectomy approach gained
popularity following the introduction of the first VATS
series in 1993.[] The VATS lobectomy technique was
defined as: No intercostal retractors; maximum utility
thoracotomy length of 8 cm; separate dissection of
the vein, arteries, and bronchi for the lobectomy; and
standard lymph node sampling or dissection in line
with the Cancer and Leukemia Group B 39802 Study
of 2007.[] All patients underwent a biportal VATS lobectomy in our present series. The mean length of
the utility thoracotomy incision was 4.7 cm and all patients
underwent a mediastinal lymph node dissection.
The advantages of a thoracoscopic lung resection are
decreased blood loss,[,] decreased pain,[,,-
] shorter hospital stay and duration of chest tube
placement,[,,,] preservation of post-operative
pulmonary functions,[,,,] diminished inflammatory
response,[] lower rate of general complications,[,] and earlier return to post-operative activity.
[] A thoracoscopic lobectomy is an approved surgical
approach in selected cases of NSCLC.[] In our study,
the hospital stay of patients who underwent a thoracoscopic
lobectomy was significantly shorter (p<0.001),
which was consistent with the literature.
Adjuvant chemotherapy on behalf of resected NSCLC
has been applied at the beginning of the 2000s. Several
randomized and clinical studies performed over the past
decade have identified the positive effect of post-operative
cisplatin-based adjuvant chemotherapy for Stage
IIA-IIIA NSCLC on survival.[-] The rate of use of
adjuvant chemotherapy, namely, compliance with chemotherapy,
has been demonstrated to be associated with
increased survival.[] Compliance with chemotherapy
can be increased through surgical resection techniques
that improve the administration of chemotherapy. In
the present study, 36 patients who underwent a thoracoscopic
lobectomy were compared with 48 patients who
underwent a lobectomy by thoracotomy. Among patients
received more than 66% of the total planned dose
of Vinorelbine and Cisplatin, respectively, in ANITA trial.[] Especially, the ratio of patients who received the
total planned dose ranged from 40% to 78.4%.[,] In
our study, the ratio of cisplatin drug dose administration
rate was 82.9% and 77.6% in the VATS and thoracotomy
groups, respectively (p=0.004); while the Nevalbine
drug dose ratio was 82.4% and 74.8% in the VATS and
thoracotomy groups, respectively (p=0.004). Although
the drug doses applied were compatible with the literature
for both groups, the dose applied in the VATS group
was significantly higher than in the thoracotomy group.
The results of the VATS lobectomy, including the duration
of hospital stay, the initiation of chemotherapy and
compliance with chemotherapy, have been shown to be
superior to the lobectomy by thoracotomy approach in
many studies published in the literature.[,,] The
duration between operation and the initiation of chemotherapy
was significantly shorter in VATS group (Table
2) (p=0.002). The duration of hospital stay, the time until
the initiation of chemotherapy, and the dose ratio of
Cisplatin and Nevalbine were found to be significantly superior in the VATS group when compared to the lobectomy
by thoracotomy group in the present study.
Definitely, a meaningful higher rate of patients chemotherapy
compliance in case of thoracoscopy compared
to thoracotomy.[,]
Table 2: Comparison of different variables between
groups
Conclusion
The thoracoscopic lobectomy approach has been
known to offer several advantages over the lobectomy
and thoracotomy approaches. The data obtained in the
present study have showed us that the VATS lobectomy
approach is a more accurate and quicker in the initiation
of chemotherapy and chemotherapy compliance.
Peer-review: Externally peer-reviewed.
Conflict of Interest: All authors declared no conflict of interest.
Ethics Committee Approval: The study was approved by
the University of Health Sciences Hamidiye Scientific Research
Ethics Committee (no: E-46418926-050.01.04--3065,
date: 15/01/2021).
Financial Support: None declared.
Authorship contributions: Concept - İ.K., Ç.T., A.Ö., L.A.,
S.E.; Design - İ.K., Ç.T., A.Ö., L.A., S.E.; Supervision - İ.K.,
Ç.T., A.Ö., L.A., S.E.; Funding - Ç.T., S.E.; Materials - A.Ö.,
Ç.T.; Data collection and/or processing - İ.K., Ç.T., S.E.; Data
analysis and/or interpretation - L.A., S.E., Ç.T.; Literature
search - İ.K., Ç.T., L.A.; Writing - A.Ö., S.E.; Critical review
- İ.K., Ç.T., S.E.
References
Roviaro G, Varoli F, Rebuffat C, Vergani C, D"Hoore
A, Scalambra SM, et al. Major pulmonary resections:
Pneumonectomies and lobectomies. Ann Thorac Surg
1993;56(3):779-83.
Paul S, Altorki NK, Sheng S, Lee PC, Harpole DH,
Onaitis MW, et al. Thoracoscopic lobectomy is associated
with lower morbidity than open lobectomy: A
propensity-matched analysis from the STS database. J
Thorac Cardiovasc Surg 2010;139(2):366-78.
Gaudet MA, D"Amico TA. Thoracoscopic lobectomy
for non-small cell lung cancer. Surg Oncol Clin N Am
2016;25(3):503-13.
Petersen RP, Pham D, Burfeind WR, Hanish SI, Toloza
EM, Harpole DH Jr, et al. Thoracoscopic lobectomy
facilitates the delivery of chemotherapy after resection
for lung cancer. Ann Thorac Surg 2007;83(4):1245-9.
Daniels LJ, Balderson SS, Onaitis MW, D"Amico TA.
Thoracoscopic lobectomy: a safe and effective strategy
for patients with stage I lung cancer. Ann Thorac Surg
2002;74(3):860-4.
McKenna RJ Jr, Houck W, Fuller CB. Video-assisted
thoracic surgery lobectomy: experience with 1,100
cases. Ann Thorac Surg 2006;81(2):421-5
Nagahiro I, Andou A, Aoe M, Sano Y, Date H, Shimizu
N. Pulmonary function, postoperative pain, and
serum cytokine level after lobectomy: a comparison of
VATS and conventional procedure. Ann Thorac Surg
2001;72(2):362-5.
Yan TD, Black D, Bannon PG, McCaughan BC. Systematic
review and meta-analysis of randomized and
nonrandomized trials on safety and efficacy of video-assisted
thoracic surgery lobectomy for early-stage non-small-
cell lung cancer. J Clin Oncol 2009;27(15):2553-62.
Yan TD, Cao C, D"Amico TA, Demmy TL, He J,
Hansen H, et al; International VATS Lobectomy Consensus
Group. Video-assisted thoracoscopic surgery
lobectomy at 20 years: a consensus statement. Eur J
Cardiothorac Surg 2014;45(4):633-9.
Su S, Scott WJ, Allen MS, Darling GE, Decker PA,
McKenna RJ, et al. Patterns of survival and recurrence
after surgical treatment of early stage non-small cell
lung carcinoma in the ACOSOG Z0030 (ALLIANCE)
trial. J Thorac Cardiovasc Surg 2014;147(2):747-52
Flores RM, Ihekweazu UN, Rizk N, Dycoco J, Bains
MS, Downey RJ, et al. Patterns of recurrence and incidence
of second primary tumors after lobectomy by
means of video-assisted thoracoscopic surgery (VATS)
versus thoracotomy for lung cancer. J Thorac Cardiovasc
Surg 2011;141(1):59-64.
Ilonen IK, Räsänen JV, Knuuttila A, Salo JA, Sihvo EI.
Anatomic thoracoscopic lung resection for non-small
cell lung cancer in stage I is associated with less morbidity and shorter hospitalization than thoracotomy.
Acta Oncol 2011;50(7):1126-32.
Douillard JY, Rosell R, De Lena M, Carpagnano F,
Ramlau R, Gonzáles-Larriba JL, et al. Adjuvant vinorelbine
plus cisplatin versus observation in patients
with completely resected stage IB-IIIA non-small-cell
lung cancer (Adjuvant Navelbine International Trialist
Association [ANITA]): a randomised controlled trial.
Lancet Oncol 2006;7(9):719-27.
Arriagada R, Bergman B, Dunant A, Le Chevalier T,
Pignon JP, Vansteenkiste J, et al. Cisplatin-based adjuvant
chemotherapy in patients with completely
resected non-small-cell lung cancer. N Engl J Med
2004;350(4):351-60.
Winton T, Livingston R, Johnson D, Rigas J, Johnston
M, Butts C, et al. Vinorelbine plus Cisplatin vs. Observation
in Resected Non?Small-Cell Lung Cancer. N
Engl J Med 2005;352(25):2589-97.
Pignon JP, Tribodet H, Scagliotti GV, Douillard JY,
Shepherd FA, Stephens RJ, et al. Lung adjuvant cisplatin
evaluation: a pooled analysis by the LACE Collaborative
Group JCO 2008;26(21):3552-9.
Swanson SJ, Herndon JE, D"Amico TA, Demmy TL,
McKenna RJ, Green MR, et al. Video-assisted thoracic
surgery lobectomy: report of CALGB 39802?A
prospective, multi-ınstitution feasibility study. JCO
2007;25(31):4993-7.
Sugiura H, Morikawa T, Kaji M, Sasamura Y, Kondo S,
Katoh H. Long-term benefits for the quality of life after
video-assisted thoracoscopic lobectomy in patients
with lung cancer. Surg Laparosc Endosc Percutan Tech
1999;9(6):403-8.
Demmy TL, Curtis JJ. Minimally invasive lobectomy
directed toward frail and high-risk patients: a casecontrol
study. Ann Thorac Surg 1999;68(1):194-200.
Nomori H, Horio H, Naruke T, Suemasu K. What is the
advantage of a thoracoscopic lobectomy over a limited
thoracotomy procedure for lung cancer surgery? Ann
Thorac Surg 2001;72(3):879-84.
Nakata M, Saeki H, Yokoyama N, Kurita A, Takiyama
W, Takashima S. Pulmonary function after lobectomy:
video-assisted thoracic surgery versus thoracotomy.
Ann Thorac Surg 2000;70(3):938-41.
Nomori H, Ohtsuka T, Horio H, Naruke T, Suemasu
K. Difference in the impairment of vital capacity and
6-minute walking after a lobectomy performed by thoracoscopic
surgery, an anterior limited thoracotomy,
an anteroaxillary thoracotomy, and a posterolateral
thoracotomy. Surg Today 2003;33(1):7?12.
Ettinger DS, Wood DE, Aisner DL, Akerley W, Bauman
J, Chirieac LR, et al. Non?small cell lung cancer, version
2017, NCCN clinical practice guidelines in oncology.
J Natl Compr Canc Netw 2017;15(4):504-35.
Lee JG, Cho BC, Bae MK, Lee CY, Park IK, Kim DJ, et
al. Thoracoscopic lobectomy is associated with superior
compliance with adjuvant chemotherapy in lung
cancer. Ann Thorac Surg 2011;91(2):344-8.
Velcheti V, Viswanathan AK, Baggstrom MQ, Govindan
R. Drug delivery and toxicity of adjuvant chemotherapy
for non-small cell lung cancer (NSCLC): Washington
University experience. Acta Oncol 2007;46(6):869-70.
Jiang G, Yang F, Li X, Liu J, Li J, Zhao H, et al. Videoassisted
thoracoscopic surgery is more favorable than
thoracotomy for administration of adjuvant chemotherapy
after lobectomy for non-small cell lung cancer.
World J Surg Oncol 2011;9:170.
Zhi X, Gao W, Han B, Yang Y, Li H, Liu D, et al. VATS
lobectomy facilitates the delivery of adjuvant docetaxel-
carboplatin chemotherapy in patients with non-small
cell lung cancer. J Thorac Dis 2013;5(5):578-84.
