Radiotherapy and Oncology 116 (2015) 257261

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Radiotherapy and Oncology

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Chemoradiotherapy of esophageal carcinoma

Clinical efcacy and failure pattern in patients with cervical esophageal

cancer treated with denitive chemoradiotherapy
Peng Zhang 1, Mian Xi 1, Lei Zhao, Bo Qiu, Hui Liu, Yong-Hong Hu, Meng-Zhong Liu
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Esophageal Cancer
Institute, Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, PR China

a r t i c l e

i n f o

Article history:
Received 21 November 2014
Received in revised form 23 June 2015
Accepted 16 July 2015
Available online 29 July 2015
Keywords:
Failure pattern
Prognosis
Cervical esophageal cancer
Chemoradiotherapy
Prognostic factor

a b s t r a c t
Background: Data on cervical esophageal cancer (CEC) based on modern radiotherapy technique are rare.
We aimed to analyze the clinical efcacy and failure pattern of patients with CEC who underwent
denitive chemoradiotherapy.
Methods: Between February 2002 and October 2013, 102 patients with CEC treated with denitive
chemoradiotherapy were retrospectively analyzed. All patients received concurrent platinum-based
chemotherapy with conformal radiotherapy (5070 Gy in 2535 fractions, 5 fractions per week over
57 weeks). Overall survival (OS), progression-free survival (PFS) and loco-regional failure-free survival
(LRFFS) were calculated.
Results: The 3-year OS, PFS and LRFFS rates for the entire sample were 39.3%, 33.6% and 35.3%,
respectively. During follow-up, 32, 26, and 41 patients had developed local, regional, and distant failure,
respectively. Sex and hoarseness were independent prognostic indicators for OS (P = 0.011, P < 0.001;
respectively) and PFS (P = 0.008, P = 0.001; respectively). Hoarseness was the only independent
prognostic factor for LRFFS (P = 0.002).
Conclusions: Distant metastasis was the most common failure pattern in CEC patients undergoing denitive chemoradiotherapy. Hoarseness was an independent prognostic factor for OS, PFS, and LRFFS.
2015 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 116 (2015) 257261

Cervical esophageal cancer (CEC) is relatively uncommon, with

an incidence rate of <1 per 100,000 [1]. The prognosis of CEC is
poor, which could be related to the delayed diagnosis and abundant lymphatic drainage of the cervical esophagus. Due to the
unique anatomical position between the lower border of the
cricoid cartilage and the thoracic esophagus inlet, CEC easily and
frequently invades upwards to the hypopharynx and downwards
to the thoracic esophagus [2].
The RTOG 85-01 trial indicated that concurrent chemoradiotherapy is currently considered the standard treatment for inoperable esophageal cancer [3]. However, loco-regional tumor control
and the prognosis for patients with esophageal cancer after concurrent chemoradiotherapy remain poor: approximately 5060%
patients fail loco-regionally due to persistent disease or local recurrence [4]. Recent conformal radiotherapy technology, including
three-dimensional
conformal
radiotherapy
(3DCRT)
and
intensity-modulated radiotherapy (IMRT), delivers high doses
accurately to the target volume in esophageal cancer, and spares
Corresponding author at: Department of Radiation, Sun Yat-sen University
Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong 510060, PR China.
E-mail address: liumengzhong@126.com (M.-Z. Liu).
1
Peng Zhang and Mian Xi contributed equally to this work.
http://dx.doi.org/10.1016/j.radonc.2015.07.011
0167-8140/ 2015 Elsevier Ireland Ltd. All rights reserved.

normal tissues [5,6]. Bedford et al. reported that conformal radiotherapy techniques could be expected to increase local tumor control by 1525% [6]. Accordingly, patients with CEC could
potentially benet from advanced conformal radiotherapy, which
might reduce toxicity and improve clinical outcomes.
Data on patients with CEC treated with 3DCRT/IMRT and concurrent chemotherapy are rare. The purpose of this study was to
analyze the clinical efcacy and failure pattern following denitive
chemoradiotherapy and to explore the possible prognostic factors
related to survival in patients with CEC.
Materials and methods
Between February 2002 and October 2013, we respectively
reviewed 102 patients diagnosed with CEC and who received
denitive chemoradiotherapy at the Sun Yat-sen University
Cancer Center. The primary tumor center was between the
cricopharyngeus muscle and the thoracic esophagus inlet [7]. All
patients had pathologically proven squamous cell carcinoma with
or without superior hypopharyngeal extension or inferior thoracic
esophageal extension. Patients recruited to our study had no distant organ metastasis or abdominal lymphadenopathy; no history
of radiotherapy or chemotherapy; and Eastern Cooperative

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Prognosis and failure pattern of CEC

Oncology Group (ECOG) performance status 63. All patients were

staged according to the sixth edition of the American Joint
Committee on Cancer (AJCC) staging system.
Patient immobilization, simulation, and treatment planning
were performed according to standard protocols for patients with
esophageal carcinoma receiving conformal radiotherapy in our
department [8]. All patients received 3DCRT or IMRT with 68
MV photon beams. A total prescription dose of 5070 Gy was delivered to gross tumor volume (GTV) in 2535 fractions, with ve fractions per week over 57 weeks. Prophylactic treatment (5054 Gy)
was delivered to the clinical target volume (CTV). GTV was dened
as the primary tumor (GTV-T) and involved lymph nodes (GTV-LN)
on the planning CT scan performed by the attending radiation
oncologist using all available resources, including barium esophagography, laryngoscopy image, and diagnostic CT image data. The
CTV included the CTV-T and CTV-LN. CTV-T was dened as the
GTV-T plus the volume of a 3-cm margin in the cranialcaudal
direction and a 1-cm radial margin. The CTV-LN encompassed the
elective nodal regions, including bilateral levels IIIV of the cervical
lymph node area, supraclavicular fossa, and upper mediastinal area.
The cranial and caudal limits of the CTV-LN were the caudal edge of
the lateral process of the atlas and trachea bifurcation, respectively
[9,10]. The planning target volume was determined by adding
0.8-cm radial margin to the CTV [8].
Induction chemotherapy (ICT) was administered using
platinum-based regimens in 18 patients (17.6%). Concurrent
chemotherapy was administered using regimens that included cisplatin plus 5-uorouracil and cisplatin plus docetaxel. Thirty-nine
patients were concurrently treated with docetaxel and cisplatin
regimens: 13 were treated with docetaxel (60 mg/m2) on Day 1
and 29, and cisplatin (80 mg/m2) on Day 1 and 29 [8]; 26 were
treated with cisplatin (30 mg/m2) and docetaxel (30 mg/m2)
weekly for at least 4 weeks [11]. Another 63 patients were concurrently treated with cisplatin (60 mg/m2) on Day 1 and 29 and with
5-uorouracil (300 mg/m2/24 h) on Day 13 and Day 2931 [12].
After the end of treatment, patients were evaluated with physical examination, barium swallow, endoscopy, and CT scan at
three-month intervals for two years, and 6 months thereafter.
The National Cancer Institute Common Toxicity Criteria (version
3.0) was used to score acute and late treatment toxicity.
Treatment failure was considered to have occurred if pathologically proven or documented radiographically by serial progression
[13]. Local failure was dened as the persistence or recurrence of
the primary tumor, and regional failure was referred to the persistence or recurrence of the regional lymph nodes [14]. Distant failure was dened as the metastasis to any site beyond the primary
tumor and regional lymph nodes. All failure patterns were analyzed regardless of the record of previous failure [13].
Progression-free survival (PFS), loco-regional failure-free survival
(LRFFS) and overall survival (OS) were dened as the time from
the diagnosis of CEC to the rst detection of tumor progression,
localregional tumor persistence or recurrence, and death from
any cause or last follow-up, respectively.
The last follow-up was on August 31, 2014. Survival analyses
were carried out using the KaplanMeier method, and differences
between curves were analyzed using the log-rank test. The Cox
proportional hazards model was used to test independent factors
of OS, PFS and LRFFS. The criterion for statistical signicance was
set at a = 0.05; P-values were determined from two-sided tests.
All statistical analyses were performed using SPSS v16.0 (SPSS,
Chicago, IL, USA).
Results
The patient characteristics are detailed in Table 1. According to
the AJCC staging system (6th edition), 32 patients had stage II

Table 1
Demographic and pathological characteristics of the study population.
Characteristic

No. of patients (%)

Age (years), median (range)

61 (3675)

Sex
Male
Female

54 (52.9%)
48 (47.1%)

ECOG performance status

01
23

92 (90.2%)
10 (9.8%)

Hypopharyngeal extension
Yes
No

23 (22.5%)
79 (77.5%)

Pathological grade
G12
G34, x

67 (65.7%)
35 (34.3%)

Weight loss
P10%
<10%

15 (14.7%)
87 (82.3%)

Hoarseness
Yes
No

12 (11.8%)
90 (88.2%)

T stage
T13
T4

58 (56.9%)
44 (43.1%)

N stage
N0
N1

18 (17.6%)
84 (82.4%)

TNM stage
II
III

32 (31.4%)
70 (68.6%)

Radiation dose (Gy)

<60
P60

12 (11.8%)
90 (88.2%)

Induction chemotherapy
Yes
No

18 (17.6%)
84 (82.4%)

Concurrent chemotherapy
Cisplatin + 5-uorouracil
Cisplatin + docetaxel

63 (61.8%)
39 (38.2%)

Abbreviations: ECOG, Eastern Cooperative Oncology Group.

disease; 70 patients had stage III disease. Fifty-six patients were

treated with 3DCRT; 46 received IMRT. The median radiation dose
was 60 Gy (range, 5070 Gy) and only 12 patients received a total
dose of <60 Gy. A total of 86 patients received radiation doses of
6066 Gy and 4 patients received >66 Gy (including three who
received 70 Gy).
At a median follow-up interval of 47 months, the 3-year OS, PFS,
and LRFFS rates for the entire sample were 39.3%, 33.6% and 35.3%,
respectively (Fig. 1). The median OS, PFS, and LRFFS were
27 months, 17 months, and 17 months, respectively. As shown in
Table 2, univariate analysis suggested that hoarseness and ICT
were signicantly associated with OS, PFS, and LRFFS. In addition,
hypopharyngeal extension (P = 0.021) was also signicantly associated with PFS. The 3-year OS, PFS, and LRFFS rates of patients with
hoarseness were signicantly worse than patients without hoarseness (0% vs. 44.7%, P < 0.001; 0% vs. 41.1%, P < 0.001; 0% vs. 43.5%,
P < 0.001; respectively). The 3-year OS, PFS and LRFFS rates of
patients who received ICT were signicantly worse than patients
who did not receive ICT (11.1% vs. 45.5%, P = 0.016; 11.1% vs.
40.5%, P = 0.019; 11.1% vs. 43.2%, P = 0.041; respectively). Clinical
variables that were statistically signicant (P < 0.1) in univariate
analysis were analyzed further in multivariate analysis with stepwise selection of variables. Multivariate analysis revealed that sex
and hoarseness were independent prognostic factors related to OS

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P. Zhang et al. / Radiotherapy and Oncology 116 (2015) 257261

Table 2
Univariate analysis of prognostic factors inuencing OS, PFS, and LRFFS in cervical
esophageal cancer.
Factor

Fig. 1. Overall survival (OS), progression-free survival (PFS) and localregional

failure-free survival (LRFFS) of the whole cohort.

and PFS. Hoarseness (HR = 2.834; P = 0.002) was the only independent prognostic factor affecting LRFFS (See Table 3).
At the time of last follow-up contact in August 2014, 32 patients
(31.4%), 26 patients (25.5%), and 41 patients (40.2%) had developed
local failure, regional failure, and distant metastasis, respectively
(Fig. 2). Forty-three patients (42.2%) experienced loco-regional failure alone. In the patients who developed distant metastasis, the
lung (27/41) was the most common site of metastasis; other sites
were bone (11/41), liver (8/41), brain (6/41), kidney (1/41), and
other distant lymph nodes (6/41).
All patients were evaluable for toxicity. The most commonly
documented treatment-related acute toxicities were nausea, vomiting, mucositis, leukopenia, and esophagitis, and the majority of
toxicities were grade 1 or 2. The most common grade 3 and 4 toxicities were mucositis, leukopenia, and gastrointestinal toxicity.
The incidence of acute grade 3 mucositis (including pharyngitis),
leukopenia, and gastrointestinal toxicity was 22.5%, 14.7%, and
24.5%, respectively. There were no treatment-related deaths, and
no patient developed acute grade 4 non-hematological toxicity.

3-year
OS
(%)

3-year
PFS
(%)

3-year
LRFFS
(%)

Age (years)
661
>61

35.0
32.9

0.176

41.7
31.5

0.228

43.9
31.5

0.059

Sex
Male
Female

34.9
40.0

0.087

32.5
40.1

0.060

37.4
36.7

0.129

ECOG PS
01
23

39.3
32.6

0.507

35.8
34.3

0.729

38.4
30.2

0.533

Weight loss
P10%
<10%

33.3
40.4

0.734

28.5
36.8

0.468

38.0
37.0

0.457

Hypopharyngeal extension
Yes
17.4
No
45.8

0.053

14.1
41.5

0.021

43.3
15.6

0.130

Primary tumor length

<4 cm
P4 cm

38.7
36.9

0.885

31.6
35.2

0.769

36.6
37.4

0.575

Hoarseness
Yes
No

0
44.7

<0.001

0
41.1

<0.001

0
43.5

<0.001

T stage
T13
T4

41.4
36.4

0.772

35.7
35.1

0.829

37.3
35.1

0.711

N stage
N0
N1

47.6
37.5

0.864

33.1
34.5

0.643

40.0
35.8

0.740

Radiation dose
<60 Gy
P60 Gy

40.0
39.3

0.730

22.5
35.6

0.965

38.2
32.3

0.631

Radiotherapy technique
IMRT
33.9
3DCRT
27.0

0.114

27.2
21.2

0.109

44.4
23.1

0.263

Inductive CT
Yes
No

0.016

11.1
40.5

0.019

11.1
43.2

0.041

0.188

27.0

0.434

26.2

0.109

11.1
45.5

Concurrent CT regimen
Cisplatin + 527.2
uorouracil
Cisplatin + docetaxel 42.2

37.6

42.3

Abbreviations: PS, performance status; CT, chemotherapy; OS, overall survival; PFS,
progression-free survival; LRFFS, localregional failure-free survival; IMRT, intensity-modulated radiotherapy; 3DCRT, three-dimensional conformal radiotherapy.

Discussion
Due to relatively low morbidity, reports on the clinical efcacy
and failure pattern of CEC treatment are limited. Previous studies
on the efcacy of radiotherapy with or without chemotherapy for
treating CEC reported 3-year survival rates of 2237.9% following
short-term observation [1518]. In this study, the 3-year OS, PFS
and LRFFS rates were 39.3%, 33.6% and 35.3%, respectively. There
were no stage IV patients in our study and all patients received
conformal radiotherapy with concurrent chemotherapy, which
may have led to a relatively higher survival rate.
Currently, there is no consensus on the CTV delineation of CEC.
At our institution, CTV-T includes the GTV-T plus the volume of a
3-cm margin in the cranialcaudal direction, in accordance with
previous reports. In previous studies, the CTV includes the GTV-T
with an additional margin varying from 2 cm to 5 cm in the cranialcaudal direction [15,19,20]. Although CEC is adjacent to the

Table 3
Multivariate analysis of prognostic factors related to OS, PFS, and LRFFS in cervical
esophageal cancer.
Endpoint

Variable

HR

95% CI for HR

OS

Sex
Hypopharyngeal extension
Hoarseness
Induction chemotherapy

1.992
1.455
3.646
1.418

1.1723.386
0.8112.608
1.7827.462
0.7462.695

0.011
0.208
<0.001
0.287

PFS

Sex
Hypopharyngeal extension
Hoarseness
Induction chemotherapy

2.039
1.659
3.503
1.201

1.2083.440
0.9163.007
1.6957.239
0.6152.346

0.008
0.095
0.001
0.591

LRFFS

Age
Hoarseness
Induction chemotherapy

1.526
2.834
1.389

0.9482.456
1.4435.567
0.7692.509

0.082
0.002
0.276

Abbreviations: OS, overall survival; PFS, progression-free survival; LRFFS, local

regional failure-free survival; 95% CI, 95% condence interval; HR, hazard ratio.

260

Prognosis and failure pattern of CEC

Fig. 2. Patterns of failure in patients with cervical esophageal cancer.

hypopharynx, the clinical characteristics and treatment results of

CEC differ from that of head and neck cancer. Considering the primary tumor site, the treatment strategy for some patients with
CEC with hypopharyngeal extension is slightly different from that
for hypopharyngeal cancer. Due to the very low morbidity of CEC,
specic reports about neck and mediastinal metastasis in CEC are
rare. Hirano et al. reported that the incidence of upper mediastinal
metastasis and cervical lymph nodal metastasis was 33.3% and
85.7%, respectively, revealing that dissection of the upper mediastinal and neck lymph nodes (levels IIIV) is necessary for improving
the cure rate [19]. In addition, the rate of regional lymph node
recurrence in patients with CEC treated with denitive radiotherapy or chemoradiotherapy varies from 0% to 25% in patients with
elective lymph node irradiation and is at least 25% in patients without elective lymph node irradiation [9]. At our institution, CTV-LN
encompassed bilateral levels IIIV of the cervical lymph node area,
supraclavicular fossa, and upper mediastinal area, which is in accordance with the previous report [9]. For patients with positive lymph
nodes (>3 cm in diameter) or patients in whom CT scans clearly
indicated muscular inltration, additional adjacent structures at
risk of tumor inltration were also included in the CTV [20]. In addition, rather than simply expanding the GTV uniformly, the CTV on
the planning CT was delineated on a slice-by-slice basis [21].
Loco-regional control remains the main challenge when treating
CEC. RTOG 94-05 revealed that, compared with 50.4 Gy, escalating
the dose to 64.8 Gy did not improve survival or loco-regional control [22], but it should be noted that RTOG 94-05 used conventional
radiotherapy with a sequential boost for dose escalation. In addition, the margins of high-dose volumes were greater than those
now considered standard practice, which might have resulted in
excessive overall toxicity. Dose escalation for enhancing local control in esophageal cancer is still being debated. Given the current
availability of conformal radiotherapy technology, which can
deliver high doses accurately to the target volume and spare normal

tissues, recent reports have demonstrated the application of dose

escalation for esophageal cancer in particular [5]. Yu et al. reported
safely achieving dose escalation of up to 70 Gy in patients with esophageal cancer, and acute toxicities were well-tolerated [5]. In
addition, the cervical esophagus is distant from organs previously
at risk, such as the lung and heart, which means normal tissues
are easily spared. He et al. retrospectively analyzed 193 patients
with esophageal squamous cell carcinoma treated with denitive
concurrent chemoradiotherapy and found that the high-dose group
(P50.4 Gy) had a signicantly lower local failure rate than the
low-dose group (<50.4 Gy) [23]. The authors recommended that
the denitive radiation dose should not exceed 50.4 Gy for middle/distal esophageal cancer, but a higher dose of >50.4 Gy could
help improve tumor local control for proximal esophageal cancer
[23]. At our institution, CEC is often treated with a protocol analogous to that used for locally advanced head and neck cancer, with
a radiation dose of 6066 Gy. In this study, only 12 patients
received a total dose of <60 Gy (at the discretion of the attending
physician or because the patient refused further radiotherapy).
Therefore, the limited number of patients means that it is unfortunate we could not compare the higher dose (70 Gy) with a relatively
lower dose (50 Gy). Yamada et al. reported that 13 of 27 patients
with CEC (48.1%) had local recurrence following treatment with
conventional radiotherapy [16]. In our study, only 32 patients
(31.4%, including 10 patients with regional and/or distant failure)
had local failure, which indicates better local control compared
with that achieved with conventional radiotherapy. Our results
indicate that the prescribed radiation dose of 6066 Gy is reasonable based on the relatively satisfactory clinical outcome and
tolerable treatment-related toxicities.
In this study, ICT did not show survival benet or improve
loco-regional control. On the contrary, patients who received ICT
had worse prognosis than those who did not. Due to the absence
of phase III clinical trials, the benet of ICT in esophageal cancer
is still being debated. The following reasons may explain why ICT
was conversely related to survival in this study. Firstly, patients
who received ICT tended to have more advanced stages of disease.
Seventeen of 70 patients with stage III disease received ICT, while
only one patient from 32 patients with stage II disease underwent
ICT (P = 0.010). Secondly, ICT extended the overall treatment time,
which has an adverse effect on prognosis. Lastly, contrary to highly
sensitive tumors such as lymphoma, the cytotoxic chemotherapy
may simply have been insufciently active for eliciting an effect
in esophageal cancer [24]. A prospective randomized trial involving ICT versus no ICT followed by denitive chemoradiotherapy
for patients with esophageal cancer is currently underway at our
institution.
In prognostic analysis, hoarseness was an independent prognostic factor for OS, PFS, and LRFFS. Patients without hoarseness had
better prognosis for survival compared to patients with hoarseness. Caused by tumor overgrowth of the left laryngeal nerve,
hoarseness is considered a late symptom of esophageal cancer
[25]. Due to the small sample size and patient heterogeneity, we
could not detect statistically signicant prognostic survival
differences for the tumor-nodes-metastasis (TNM) stage.
The potential limitations of our study are the nature of a retrospective analysis, relatively small sample size, and that it was a
single-institution experience. Given the rarity of this diagnosis,
larger multi-center prospective studies should be carried out to
conrm these preliminary results and to test the effect of advances
in radiotherapy.
In summary, distant metastasis was the most common failure
pattern in CEC patients undergoing denitive chemoradiotherapy.
Hoarseness was an independent prognostic factor for OS, PFS,
and LRFFS.

P. Zhang et al. / Radiotherapy and Oncology 116 (2015) 257261

Funding source
This work was supported by a grant from the Sci-Tech Project
Foundation of Guangdong Province (Grant No. 2012B031800287).
Conicts of interest
The authors have declared no conicts of interest.
References
[1] Davies L, Welch HG. Epidemiology of head and neck cancer in the United
States. Otolaryngol Head Neck Surg 2006;135:4517.
[2] Daiko H, Hayashi R, Saikawa M, Sakuraba M, Yamazaki M, Miyazaki M, et al.
Surgical management of carcinoma of the cervical esophagus. J Surg Oncol
2007;96:16672.
[3] Herskovic A, Martz K, Al-Sarraf M, Leichman L, Brindle J, Vaitkevicius V, et al.
Combined chemotherapy and radiotherapy compared with radiotherapy alone
in patients with cancer of the esophagus. N Engl J Med 1992;326:15938.
[4] Liao Z, Cox JD, Komaki R. Radiochemotherapy of esophageal cancer. J Thorac
Oncol 2007;2:55368.
[5] Yu W, Cai XW, Liu Q, et al. Safety of dose escalation by simultaneous integrated
boosting radiation dose within the primary tumor guided by 18FDG-PET/CT for
esophageal cancer. Radiother Oncol 2015;114:195200.
[6] Bedford JL, Viviers L, Guzel Z, Childs PJ, Webb S, Tait DM. A quantitative
treatment planning study evaluating the potential of dose escalation in
conformal radiotherapy of the oesophagus. Radiother Oncol 2000;57:18393.
[7] Gkika E, Gauler T, Eberhardt W, Stahl M, Stuschke M, Pttgen C. Long-term
results of denitive radiochemotherapy in locally advanced cancers of the
cervical esophagus. Dis Esophagus 2014;27:67884.
[8] Li QQ, Liu MZ, Hu YH, Liu H, He ZY, Lin HX. Denitive concomitant
chemoradiotherapy with docetaxel and cisplatin in squamous esophageal
carcinoma. Dis Esophagus 2010;23:2539.
[9] Van De Voorde L, Larue RT, Pijls M, et al. A qualitative synthesis of the evidence
behind elective lymph node irradiation in oesophageal cancer. Radiother Oncol
2014;113:16674.
[10] Grgoire V, Levendag P, Ang KK, et al. CT-based delineation of lymph node
levels and related CTVs in the node-negative neck: DAHANCA, EORTC, GORTEC,
NCIC, RTOG consensus guidelines. Radiother Oncol 2003;69:22736.
[11] Day FL, Leong T, Ngan S, Thomas R, Jefford M, Zalcberg JR, et al. Phase I trial of
docetaxel, cisplatin and concurrent radical radiotherapy in locally advanced
oesophageal cancer. Br J Cancer 2011;104:26571.

261

[12] Liu H, Lu L, Zhu Q, Hao Y, Mo Y, Liu M, et al. Cervical nodal metastases of

unresectable thoracic esophageal squamous cell carcinoma Characteristics of
long-term survivors after concurrent chemoradiotherapy. Radiother Oncol
2011;99:1816.
[13] Welsh J, Settle SH, Amini A, Xiao L, Suzuki A, Hayashi Y, et al. Failure patterns
in patients with esophageal cancer treated with denitive chemoradiation.
Cancer 2012;118:263240.
[14] Cao CN, Liu SY, Luo JW, et al. Pattern of failure in surgically treated patients
with cervical esophageal squamous cell carcinoma. Otolaryngol Head Neck
Surg 2014;151:2604.
[15] Huang SH, Lockwood G, Brierley J, et al. Effect of concurrent high-dose
cisplatin chemotherapy and conformal radiotherapy on cervical esophageal
cancer survival. Int J Radiat Oncol Biol Phys 2008;71:73540.
[16] Yamada K, Murakami M, Okamoto Y, Okuno Y, Nakajima T, Kusumi F, et al.
Treatment results of radiotherapy for carcinoma of the cervical esophagus.
Acta Oncol 2006;45:11205.
[17] Stuschke M, Stahl M, Wilke H, Walz MK, Oldenburg AR, Stben G, et al.
Induction chemotherapy followed by concurrent chemotherapy and high-dose
radiotherapy for locally advanced squamous cell carcinoma of the cervical
oesophagus. Oncology 1999;57:99105.
[18] Wang S, Liao Z, Chen Y, et al. Esophageal cancer located at the neck and upper
thorax treated with concurrent chemoradiation: a single-institution
experience. J Thorac Oncol 2006;1:2529.
[19] Hirano S, Nagahara K, Moritani S, Kitamura M, Takagita S. Upper mediastinal
node dissection for hypopharyngeal and cervical esophageal carcinomas. Ann
Otol Rhinol Laryngol 2007;116:2906.
[20] Grgoire V, Eisbruch A, Hamoir M, Levendag P. Proposal for the delineation of
the nodal CTV in the node-positive and the post-operative neck. Radiother
Oncol 2006;79:1520.
[21] David MB, Eisbruch A. Delineating neck targets for intensity-modulated
radiation therapy of head and neck cancer. Front Radiat Ther Oncol
2011;43:25570.
[22] Minsky BD, Pajak TF, Ginsberg RJ, et al. INT 0123 (Radiation Therapy Oncology
Group 9405) phase III trial of combined-modality therapy for esophageal
cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol
2002;20:116774.
[23] He L, Allen PK, Potter A, et al. Re-evaluating the optimal radiation dose for
denitive chemoradiotherapy for esophageal squamous cell carcinoma. J
Thorac Oncol 2014;9:1398405.
[24] Glynne-Jones R, Hoskin P. Neoadjuvant cisplatin chemotherapy before
chemoradiation: a awed paradigm? J Clin Oncol 2007;25:52816.
[25] Higuchi K, Koizumi W, Tanabe S, Sasaki T, Katada C, Azuma M, et al. Current
management of esophageal squamous-cell carcinoma in Japan and other
countries. Gastrointest Cancer Res 2009;3:15361.