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Hyperfractionated Irradiation with 3 Cycles of Induction
Chemotherapy in Stage IIIA-N2 Lung Cancer
Fengshi Chen •Kenichi Okubo •Makoto Sonobe •Keiko Shibuya •
Yukinori Matsuo •Young Hak Kim •Kazuhiro Yanagihara •Toru Bando •
Hiroshi Date
Published online: 28 August 2012
ÓSocie
´te
´Internationale de Chirurgie 2012
Abstract
Background The purpose of the present study was to
improve the prognosis of patients with stage IIIA-N2 non-
small cell lung cancer (NSCLC). To achieve that goal, we
performed induction chemoradiotherapy followed by
surgery.
Methods The criteria for this phase II study were
B75-year-old patients with pathologically diagnosed stage
IIIA-N2 NSCLC who had performance statuses of 0 or 1
with good organ function. Three cycles of chemotherapy
with paclitaxel and carboplatin were carried out, with
concurrent hyperfractionated irradiation (42 Gy). After re-
evaluation, pulmonary resections were considered unless
patients showed progressive disease. The primary endpoint
was overall survival (OS), and the secondary endpoints
were disease-free survival (DFS) and absence of toxicity.
Results All 22 patients enrolled in this study completed
the induction chemoradiotherapy without any severe
complications. In these 22 patients, the 2- and 5-year OS
were 81 and 47 %, respectively. There were no therapy-
related deaths. Surgery was subsequently performed in 19
patients (86 %). Pathological complete responses were
seen in 6 patients (27 %), while node downstaging was
obtained in 10 patients (45 %). In the 19 patients who
underwent surgery, the 2- and 5-year OS rates were 83 and
62 %, respectively, and the 2-year DFS rate was 63 %. All
6 patients with pathological complete responses survived
without disease. Patients with residual multiple-station N2
showed worse OS and DFS rates than did those with
downstaged and single-station N2 (P=0.026 and
P\0.0001, respectively).
Conclusions This trimodal therapy was effective and well
tolerated, and it is an acceptable therapeutic option for
patients with locally advanced stage IIIA-N2 NSCLC.
Patients without persistent multiple-station N2 showed
promising survival.
Introduction
Some studies of induction chemoradiotherapy (CRT) fol-
lowed by surgery have obtained promising results for
patients with locally advanced non-small cell lung cancer
(NSCLC) [1–5]; however, the standard treatment for
NSCLC remains concurrent CRT [6,7]. Two large multi-
center randomized phase III trials recently investigated the
role of local therapy in stage IIIA-N2 NSCLC [1,8]. The
EORTC 08941 study compared resections with radiother-
apy after patients exhibited response to induction chemo-
therapy [8], while the North American Intergroup 0139
trial compared surgery after CRT with CRT alone [1].
F. Chen K. Okubo M. Sonobe T. Bando H. Date (&)
Department of Thoracic Surgery, Kyoto University,
54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
e-mail: hdate@kuhp.kyoto-u.ac.jp
F. Chen
e-mail: fengshic@kuhp.kyoto-u.ac.jp
K. Shibuya Y. Matsuo
Department of Radiation Oncology and Image-Applied Therapy,
Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku,
Kyoto 606-8507, Japan
Y. H. Kim
Department of Respiratory Medicine, Kyoto University,
54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
K. Yanagihara
Outpatient Oncology Unit, Kyoto University, Kyoto, Japan
123
World J Surg (2012) 36:2858–2864
DOI 10.1007/s00268-012-1747-1
Neither study showed a significant survival benefit for
patients in the surgery arm versus those undergoing CRT
only. Surgery after CRT remains controversial for patients
with stage IIIA-N2 NSCLC; however, it should be
emphasized that progression-free survival was better in the
surgery arm in the North American Intergroup 0139 trial
[1]. Thus, if there are no or at least fewer surgery-related
deaths, a better overall survival (OS) rate might be
obtained. The aim of the present study was to evaluate the
feasibility and efficacy of combination chemotherapy with
carboplatin–paclitaxel and concurrent radiotherapy, fol-
lowed by surgical resection for patients with locally
advanced stage IIIA-N2 NSCLC.
Patients and methods
Eligibility criteria
The criteria for study entry included the following:
(1) pathologically diagnosed NSCLC excluding low-grade
malignancies such as carcinoid, adenoid cystic carcinoma,
and mucoepidermoid carcinoma; (2) stage IIIA with his-
tologically or cytologically proven N2 disease; (3) patient
age B75 years; (4) Eastern Cooperative Oncology Group
performance status of 0 or 1; and (5) adequate bone mar-
row function (leukocyte count, C4,000/lL; neutrophil
count, C2,000/lL; hemoglobin level, C8.0 g/dL; and
platelet count, C100,000/lL), renal function (serum cre-
atinine level, \1.5 mg/dL, and blood urea nitrogen level,
B25 mg/dL), hepatic function (total serum bilirubin levels
less than the upper limit of the normal range, levels of
alanine aminotransferase and aspartate aminotransferase
less than or equal to twice the upper limits of the respective
normal ranges), and pulmonary function (partial pressure
of oxygen [PaO
2
]C65 mmHg). Written informed consent
was obtained from all patients.
Treatment protocol
The institutional review board (IRB) approved this pro-
spective phase II study. All cases were initially discussed at
multidisciplinary meetings. Prior to treatment initiation,
potential resectability was evaluated in all patients. The
pretreatment evaluation included a baseline history and
physical examination, complete blood cell counts with
differential, and routine chemistry profiles, urinalysis, chest
radiography, chest and abdominal computed tomography
(CT), bronchoscopy, brain magnetic resonance imaging
(MRI) or CT, electrocardiography, and whole-body fluoro-
2-deoxy-D-glucose positron emission tomography (FDG-
PET). Pathological proof of N2-NSCLC was confirmed
in all patients by mediastinoscopy or endobronchial
ultrasound-transbronchial needle aspiration (EBUS-TBNA).
After the pretreatment evaluation, treatment was initiated
and consisted of one course of carboplatin (area under the
curve [AUC] =6) and paclitaxel (175 mg/m
2
)onday1.
Subsequently, carboplatin (AUC =2) and paclitaxel
(45 mg/m
2
) were administered on days 22, 29, and 36.
Finally, carboplatin (AUC =6) and paclitaxel (175 mg/m
2
)
were given again on day 50. All chemotherapy agents were
administered as an intravenous infusion. Antiemetics were
used on a regular basis, including ondansetron HCl and
dexamethasone.
Radiation therapy began on day 22 in conjunction with
the administration of systemic chemotherapy. Hyperfrac-
tionated three-dimensional conformal radiation therapy
was administered with a fractional dose of 1.5 Gy twice a
day for 5 days each week. The duration between fractions
was 6 h or more. A total of 42 Gy (28 fractions) was
delivered to the primary tumor, metastatic lymph nodes,
and elective nodal area. The elective area consisted of the
ipsilateral hilar, ipsilateral mediastinal, and subcarinal
lymph nodes. The spinal cord was excluded from the
irradiation field after 39 Gy was delivered.
The blood cell counts and chemistry panels were examined
at least once a week. Patients were not to receive prophylactic
granulocyte-colony stimulating factor (G-CSF) during any
cycle. The use of G-CSF was allowed only for patients who had
an absolute neutrophil count\0.5 910
9
/L, neutropenic fever,
or documented infections while being neutropenic. Chemo-
therapy was discontinued if the treatment outcome was pro-
gressive disease or if intolerable toxicity developed at any time.
Two weeks after the last round of chemotherapy, evalua-
tion of the disease was performed with a CT of the chest and
abdomen. PET-CT was preferred, but not mandatory. Brain
MRI or CT scans were performed again to detect latent brain
metastasis. Surgical resection was considered unless the
patient showed progressive disease. At 3–5 weeks after the
last round of chemotherapy, surgical extirpation was con-
ducted to achieve complete resection. Unilateral mediastinal
lymph node dissections were performed with all pulmonary
resections.
This study was approved by the ethics committee of
Kyoto University Graduate School of Medicine (C-85), and
was conducted in accordance with the Ethical Guidelines
for Clinical Studies by the Ministry of Health, Labour and
Welfare, Japan (July 30, 2003, amended December 28,
2004) and the Helsinki Declaration of the World Medical
Association.
Toxicity, response evaluation, and follow-up
Acute toxicities were assessed and graded according to the
Common Terminology Criteria for Adverse Events version
3.0, and late toxicity associated with thoracic radiotherapy
World J Surg (2012) 36:2858–2864 2859
123
that occurred [90 days after the start of radiotherapy was
graded according to the Radiation Therapy Oncology
Group late toxicity criteria. Nonhematological toxicities
included neurotoxicity of grade C3, esophagitis of grade
C3, radiation pneumonitis of grade C2, and dermatitis of
grade C3. The radiological response rate was evaluated
according to the Response Evaluation Criteria in Solid
Tumors [9] 2 weeks after the end of induction CRT with
chest and abdominal CT scans. After curative resection, the
patients were followed by periodic re-evaluations, which
included chest CT scans, as well as systemic surveys every
6 months for the first 3 years. All patients who had
received at least one cycle of chemotherapy were assessed
for response, toxicity, and survival.
Statistical analysis
We performed this clinical trial in an effort to improve the
prognosis of patients with stage IIIA-N2 NSCLC. The trial
was designed as a phase II study with OS as the primary
endpoint. Disease-free survival (DFS) and toxicity comprised
the secondary endpoints. Overall survival duration was cal-
culated from the first day of treatment until death due to any
cause or until the last follow-up (censored). Disease-free
survival duration was calculated from the first day of treatment
until the firstevidence of recurrence, death due to any cause, or
until the last follow-up (censored).
The sample size was initially calculated based on the
assumption of an expected 5-year survival rate of 40 % versus
a threshold value of 20 %. To attain 90 % power with a one-
sided aerror of 0.05, the required sample size was at least 42
patients. Hence, the initial study design envisioned the
enrollment of 50 fully eligible patients. Statistical analyses
were performed using the StatView (version 4.5) software
package (Abacus Concepts, Berkeley, CA, USA). The post-
operative survival rate was analyzed using the Kaplan–Meier
method. The prognostic influence of a number of variables
(age, gender, histology, radiological and pathological
response rates, pathological downstaging, and number of
residual N2 lymph node stations after treatment) on survival
was analyzed using the log rank test for univariate analyses.
Differences were considered significant at Pvalues\0.05.
Results
Patient characteristics
From June 2006 to June 2010, 22 patients with pathologically
proven stage IIIA-N2 NSCLC diseases were enrolled in this
IRB-approved phase II clinical trial before its closure due to
slow accrual. All 22 patients could be assessed for survival,
response, and toxicity. Patient characteristics are summarized
in Table 1. The 22 patients consisted of 16 men and 6 women,
with a median age of 66 years (range: 47–74 years). The
pathological proof of N2-NSCLC was obtained using EBUS-
TBNA in 9 patients and using mediastinoscopy in 13 patients.
Induction CRT
All patients finished the induction CRT without any sche-
dule delays. Of the 22 patients, 14 (64 %) exhibited a
partial response, 5 (23 %) had stable disease, and 3 (13 %)
had progressive disease, for an overall response rate of
64 % (Table 2). Of the 3 patients with progressive disease,
one patient developed contralateral mediastinal lymph
node metastases and another developed ipsilateral supra-
clavicular lymph node metastases. The remaining patient
exhibited brain metastases after induction CRT.
Toxicity of the induction CRT
Hematological toxicity was evaluable for all courses. The
following grade 3/4 toxicities were reported in 17 patients
(77 %): grade 3/4 anemia in 5 patients (23 %), grade 3/4
thrombocytopenia in 5 patients (23 %), and grade 3/4
leukocytopenia in 17 patients (77 %). Red blood cell
transfusions were given to 3 symptomatic patients (14 %).
Two patients (9 %) suffered from grade 3 acute esopha-
gitis. One patient had grade 3 radiation pneumonitis (5 %).
No patients had dermatitis of grade [2. Neurotoxicities of
grade \2 were seen in 7 patients (32 %). No life-
threatening esophagitis or clinically significant radiation
pneumonitis was observed.
Table 1 Patient characteristics Number of
patients
22
Age (years) 47–74
(median:
66)
Gender
Male 16
Female 6
Performance
status
022
10
Histological type
Adenocarcinoma 11
Squamous cell
carcinoma
11
Clinical stage
T1N2M0 6
T2N2M0 12
T3N2M0 4
2860 World J Surg (2012) 36:2858–2864
123
Surgery
Of the 22 patients, 19 patients (86 %), excluding the 3
patients who showed progressive disease after CRT,
underwent thoracotomy. Complete resections were per-
formed in all patients who underwent thoracotomy. The
following were performed: lobectomy in 13 patients,
bilobectomy in 2 patients, sleeve lobectomy in 3 patients,
and left pneumonectomy in 1 patient. The bronchial stump
was covered with intercostal muscle after each lobectomy
or pneumonectomy. The postoperative morbidity rate was
42.1 %, including bronchial fistulas in 2 patients, pro-
longed air leakage for[7 days in 2 patients, empyema in 1
patient, a chylothorax in 1 patient, atrial fibrillation in 1
patient, and congestive heart failure in 1 patient. There
were no treatment-related deaths.
Pathological findings
As shown in Table 2, there were 6 pathological complete
responses (Ef 3: no viable tumor cells in resected speci-
mens), and some degree of pathological response was
recognized in all of the remaining patients (Ef 2: \1/3
viable tumor cells [10 patients]; Ef 1: C1/3 viable tumor
cells [3 patients]). Ten patients (53 %) showed no patho-
logically positive lymph nodes after CRT (ypN0),
4 patients (21 %) exhibited only one-station pathologically
positive mediastinal lymph nodes after CRT (single-station
ypN2), and 5 patients (26 %) exhibited multiple-station
ypN2. Pathological downstaging (pN2 to ypN1 or ypN0)
occurred in 10 of the 22 enrolled patients (46 %).
Survival and recurrence
The 2- and 5-year OS rates of the 22 enrolled patients were
81 % (95 % confidence interval [CI], 64–98) and 47 %
(95 % CI, 19–75), respectively. There were no therapy-
related deaths. Surgery was subsequently performed in 19
patients (86 %). The 5-year OS in patients who were able
to undergo surgery after induction CRT was 62 %, while
that in patients who could not was 0 %. Patients who could
undergo surgery tended to survive longer than those who
could not, but there was no significant difference between
them (P=0.09; Fig. 1). The 3 patients who could not
undergo surgery died of lung cancer. The median obser-
vation time after the initiation of induction CRT was
31 months (range: 16–65 months). The calculated OS and
DFS rates at 2 years for the resected patients were 82.6 and
62.7 %, respectively (Fig. 1). In addition, the calculated
OS and DFS rates at 3 years for the resected patients were
74.4 and 54.9 %, respectively (Fig. 1). Recurrence devel-
oped in 8 (42 %) of the 19 resected patients. The first
recurrence site was not locoregional in 7 patients (brain in
2 patients, liver in 1 patient, brain and liver in 1 patient,
brain and bone in 1 patient, multiple contralateral lung in 1
patient, and multiple bilateral lungs in 1 patient). In con-
trast, liver, lung, and mediastinal/abdominal lymph node
recurrences were detected simultaneously in 1 patient.
Prognostic factors
The univariate analysis results of OS and DFS in patients
who underwent pulmonary resection after induction CRT
Table 2 Response after
induction chemoradiotherapy
(CRT)
Number of
patients
Radiological response
Complete
response
0
Partial
response
14 (64 %)
Stable
disease
5 (23 %)
Progressive
disease
3 (13 %)
Sum 22
Pathological response
Ef 3 6 (32 %)
Ef 2 10 (53 %)
Ef 1 3 (15 %)
Sum 19
Station number
of residual lymph
node after CRT
0 10 (53 %)
1 4 (21 %)
C2 5 (26 %)
Sum 19
Fig. 1 Comparison of overall survival between patients who were
able to undergo surgery after induction chemoradiotherapy (CRT) and
those who were not. Patients who underwent surgery after CRT
tended to survive longer than those who did not, but there was no
significant difference between the two groups (P=0.09)
World J Surg (2012) 36:2858–2864 2861
123
for stage IIIA-N2 NSCLC are shown in Table 3. According
to the univariate analysis of OS with various perioperative
variables, residual multiple-station N2 disease after treat-
ment (ypN2) was the only significant adverse prognostic
factor (P=0.026; Table 3). Patients with residual multi-
ple-station N2 disease after treatment (ypN2) showed
worse DFS than did those with downstaged and single-
station ypN2 (P\0.0001; Table 3). In addition, patients
with squamous cell carcinoma exhibited better DFS than
did those with adenocarcinoma (P=0.0055; Table 3).
Furthermore, all patients with Ef 3 response survived
without disease for a median follow-up time of 25 months
(range: 16–65 months), while the 5-year OS and 2-year
DFS of the patients with Ef 1 and Ef 2 responses were 51
and 46 %, respectively (Table 3).
Discussion
Surgery is an effective treatment for localized NSCLC, but
the 5-year survival rate for patients with clinical stage III
disease is \15 % [10]. Several combined treatment
modalities have been used in an attempt to decrease the
high rates of local recurrence and distant metastasis [11].
Although postoperative adjuvant chemotherapy has been
shown to significantly improve survival by meta-analysis
and clinical trials [12–14], the reported results have not
fully satisfied clinicians. Some phase II studies of induction
CRT followed by surgery have obtained promising results
[1–5]. However, the feasibility of complete resection with
the currently documented mortality and morbidity rates is
not universally accepted. Thus, we decided to perform the
present study in order to evaluate the feasibility and effi-
cacy of induction CRT.
Our study revealed that induction CRT followed by a
complete surgical resection for locally advanced IIIA-N2
NSCLC provided promising survival with an acceptable
morbidity. Our multidisciplinary treatments consisted of
carboplatin–paclitaxel chemotherapy, concurrent hyper-
fractionated three-dimensional conformal 42 Gy irradia-
tion, and surgery. Although cisplatin/etoposide therapy has
been historically used for induction therapy, the optimal
protocol for chemotherapy remains undefined in induction
CRT for locally advanced NSCLC [4,15]. A recent study
reported that carboplatin–paclitaxel therapy demonstrated a
survival rate equivalent to that of cisplatin/etoposide ther-
apy, and with a better quality of life [16,17]. Induction
CRT with carboplatin and paclitaxel has already been
reported with acceptable results for patients with stage
IIIA-N2 NSCLC [18,19]. Yokomise et al. [20] also
obtained outstanding outcomes using taxane–carboplatin
chemotherapy in patients with bulky cN2 and N3 NSCLC.
Most protocols using carboplatin–paclitaxel consist of two
cycles of chemotherapy as induction therapy [18,20], but
we chose to perform three cycles of chemotherapy before
surgery. Hyperfractionated irradiation delivers more bio-
logically effective doses in the same duration. We sought
higher effects with induction chemoradiotherapy because
reports have indicated that patients with larger responses
exhibited better prognoses [20]. However, it might be
difficult to clarify whether the three cycles of preoperative
chemotherapy or the hyperfractionated irradiation con-
tributed to the better prognosis observed in our study.
A more detailed study needs to be performed.
One earlier study reported that induction CRT is associated
with a significantly higher incidence of major postoperative
complications compared to induction chemotherapy alone
[21]. Surgical mortality after induction CRT has been shown
to be 4–11 % [1–5,8]; however, there were no treatment-
related deaths in our study. One possible reason for the
absence of treatment-related deaths is that only one patient
underwent a pneumonectomy. We performed sleeve lobec-
tomy in 3 patients (16 %) to preserve pulmonary function. We
also performed a pulmonary arterioplasty in 2 patients (11 %)
to avoid pneumonectomy. A pneumonectomy is a major
Table 3 Univariate analysis of overall survival and disease-free
survival in patients undergoing pulmonary resection after induction
chemoradiotherapy for stage IIIA-N2 non-small cell lung cancer
Number Overall
survival
Disease-free
survival
Pvalue Pvalue
Age (years)
C64 9 0.72 0.36
\64 10
Gender
Male 5 0.80 0.22
Female 14
Histological type
Adenocarcinoma 9 0.13 0.0055
Squamous cell
carcinoma
10
Radiological response rate
Partial response 14 0.62 0.42
Stable disease 5
Pathological response rate
Ef 1, 2 13 NA NA
Ef 3 6
Pathological downstaging
Yes 10 0.61 0.26
No 9
Number of residual N2-lymph node station after treatment
0–1 14 0.026 \0.0001
C25
CRT chemoradiotherapy, NA not applicable
2862 World J Surg (2012) 36:2858–2864
123
mortality risk factor, as the Intergroup 0139 trial reported a
26 % operative mortality rate in patients undergoing pneu-
monectomy [1]. However, the findings of Weder et al. [22]
consisting of a mortality rate of 3 %, dispute the potentially
high mortality risk in pneumonectomy.
Preoperative radiation therapy causes radiation pneu-
monitis and disturbs postoperative bronchial healing. In our
study, only 1 patient had grade 3 radiation pneumonitis.
Radiotherapy was stopped at 42 Gy in our protocol because
of the International Association for the Study of Lung
Cancer consensus reports that the dose of 45 Gy of
radiotherapy should not be exceeded at conventional frac-
tions before surgery [3]. However, 2 of 19 patients
exhibited bronchial fistulas. In both cases, the bronchial
fistula occurred within 1 month after discharge, and the
fistula was successfully closed during rethoracotomy. After
the development of bronchial fistula in these 2 patients, we
tried to obtain an intercostal muscle flap with a good blood
supply by preparing the flap before placing the chest
opener in the intercostal space. All complications other
than these events were resolved without difficulty by reg-
ular medical treatment. Dedicated perioperative manage-
ment could obtain a low non-hematological toxicity rate
and an absence of treatment-related deaths. Patient quality
of life was also maintained during treatment.
One of the technical difficulties faced during surgery of
these patient subsets is mediastinal node dissection result-
ing from dense peritracheal fibrosis and sclerosis after
CRT. In the patients who underwent mediastinoscopic
node biopsy for N2 staging of lung cancer, cotton-type
collagen was inserted anterior and lateral to the trachea at
the end of mediastinoscopy to separate the mediastinal
nodes from the trachea and simplify the node dissection
after induction CRT [23].
Downstaging, such as Ef 3 and ypN0, had been one of
the predictors of better outcome in earlier studies [15]. In
our series of patients, the 5-year survival rate with down-
staging and single-station ypN2 was 81.5 %, and that of the
patients with multiple-station ypN2 was 0 %. Residual
mediastinal lymph node station number after treatment
(ypN2 station number) was a significant prognostic factor
both for OS and DFS. Interestingly, in terms of lymph node
disease after CRT, patients with single-station ypN2
showed the best OS, and 2 patients with ypN0 died of brain
metastasis. A subset of patients could benefit from surgical
resection after CRT even if they showed residual N2 dis-
ease. All of the patients with complete responses survived
without disease in our study, although statistical analysis
was not applicable.
In terms of tumor histology, patients with squamous cell
carcinoma showed significantly better DFS rates than did
those with adenocarcinoma. This could be explained by the
fact that 5 of 6 patients with Ef 3 responses had squamous
cell carcinoma; however, there have been no reports on the
histological preference of carboplatin-paclitaxel therapy as
induction CRT agents for locally advanced NSCLC. Fur-
ther studies are required to confirm our results.
This study had several limitations. First, it had to be
closed because of poor accrual. The sample size of this
study was only 22, although we intended to include a larger
number of cases. This small sample size created the large
discrepancy between the two populations of patients: those
in whom surgery after induction CRT could be performed,
and those in whom it could not. Even if we had accumu-
lated more patients, this discrepancy would have remained.
Second, because this study was accomplished in a single
center, a multi-institutional phase III study is expected to
draw conclusive results. The 5-year OS rate of induction
CRT for patients with locally advanced stage IIIA-N2
NSCLC was recently reported to be 20–30 % [1–5]. The
OS rate of 62 % in our study should be carefully inter-
preted because of the limited number of cases, which may
lead to statistical bias. Most trials in stage III substantially
lack invasive and proven staging procedures, whereas all of
the patients in the present study had N2 diseases that were
histologically proven using EBUS or mediastinoscopy.
Therefore, more studies that include patients with accurate
pathologic staging are required to improve treatment
options for this patient subset.
In conclusion, chemotherapy with carboplatin and pac-
litaxel and concurrent radiotherapy as induction treatment
followed by surgical resection for selected patients with
stage IIIA-N2 NSCLC is feasible and appears to be a
promising new treatment modality. Patients without per-
sistent multiple-station N2 disease after treatment showed a
promising survival rate. A multi-institutional trial is
required to establish the effectiveness of this induction
treatment for patients with locally advanced NSCLC.
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