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C 2013 The American Laryngological,
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Rhinological and Otological Society, Inc.
Elective Central Compartment Neck Dissection in Patients With
Papillary Thyroid Carcinoma Recurrence
Omer Trivizki, MD; Moran Amit, MD; Dan M. Fliss, MD; Ziv Gil, MD, PhD
Objectives/Hypothesis: To investigate the role of elective central compartment neck dissection (CND) in patients with
recurrent papillary thyroid carcinoma in the jugular chain lymph nodes.
Study Design: Retrospective medical record review and analysis of survival outcomes.
Methods: The study was conducted at Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University.
Fifty-one patients who had prior thyroidectomy underwent therapeutic lateral neck dissection (LND) without radiological
evidence of central neck metastases. Therapeutic LND without elective CND was performed in 17 patients, and 34 patients
had elective CND. The clinical variables were similar in both groups. The median follow-up was 44 months. Disease-free survival and overall survival were the main outcome measures.
Results: The recurrence rate in the central neck was 9% (n 5 3/34) in patients undergoing CND and 12% (n 5 2/17)
in patients without CND. The overall recurrence rate was 18% (6/34) in patients with CND and 36% (6/17) in patients without CND (P 5 0.16). The 5-year disease-free survival rate was 82% and 65% in patients with or without CND, respectively
(P 5 0.69). Long-term thyroglobulin levels and complication rates were similar in both groups.
Conclusions: The lack of significant disease-free survival advantage demonstrates the need for a prospective evaluation
of the common practice of this disease.
Key Words: Thyroid, papillary, neck dissection, lymph node metastases, paratracheal.
Level of Evidence: 4.
Laryngoscope, 123:1564–1568, 2013
INTRODUCTION
The incidence of thyroid carcinoma has increased in
the last decade, mostly due to widespread use of imaging
modalities, although with no concomitantly significant
impact on survival.1 Surgery continues to be the routine
management of carcinomas originating in the thyroid
From the Department of Otolaryngology (O.T., M.A., Z.G.), Rambam
Medical Center, Rappaport School of Medicine, the Technion, Israel
Institute of Technology, Haifa, Israel, Laboratory for Applied Cancer
Research (O.T., M.A., Z.G.), Tel Aviv Sourasky Medical Center, Sackler
School of Medicine, Tel Aviv University, Tel Aviv, Israel, Department of
Otolaryngology–Head and Neck Surgery Unit (D.M.F.), Tel Aviv Sourasky
Medical Center, Sackler School of Medicine, Tel Aviv University, Tel
Aviv, Israel.
Editor’s Note: This Manuscript was accepted for publication
December 17, 2012.
Dr. Trivizki has full access to all of the data in the study and takes
responsibility for the integrity of the data and the accuracy of the data
analysis. The study was performed in partial fulfillment of the MD thesis
requirements of the Sackler Faculty of Medicine, Tel Aviv University (O.T.).
This research was supported by the Legacy Heritage Biomedical
Science Partnership Program of the Israel Science Foundation (No.
1680=08), the Israel Cancer Association (grant donated by Ellen and
Emanuel Kronitz in memory of Dr. Leon Kronitz, No. 20090068), the Israeli Ministry of Health (No. 3-7355), the Weizmann Institute–Sourasky
Medical Center Joint Grant, the Tel Aviv Sourasky Intramural Grant,
the ICRF Barbara S. Goodman Endowed Research Career Development
Award (2011-601-BGPC), and a grant from the US–Israel Binational Science Foundation (No. 2007312) to Dr. Ziv Gil.
The authors have no other funding, financial relationships, or conflicts of interest to disclose.
Send correspondence to Ziv Gil, MD, Department of Otolaryngology, Rambam Medical Center, Rappaport School of Medicine, the Technion, Israel Institute of Technology, Haifa, Israel.
E-mail: [email protected]
DOI: 10.1002/lary.23982
Laryngoscope 123: June 2013
1564
gland. Well-differentiated thyroid carcinomas (WDTCs),
including papillary thyroid carcinoma (PTC), require
resection of the primary tumor and clearance of clinically evident nodal metastases. The primary echelons for
malignant tumors of the thyroid are the paratracheal
and superior mediastinum lymph nodes (levels VI and
VII). It is generally accepted that palpable neck disease
or radiological evidence of nodal metastases in PTC will
necessitate therapeutic neck dissection; however, there
is no level 1 evidence supporting the rationale for performing prophylactic neck dissection in PTC.
We approached the question of whether an elective
central compartment neck dissection (CND) should be
performed in patients who had prior thyroidectomy and
presented with jugular chain metastases, by investigating specific outcome measures, including disease-free
survival, recurrence rate, and morbidity, in two groups
of patients: those undergoing therapeutic lateral neck
dissection (LND) and elective CND and those undergoing LND alone. This is the first study to compare the
early outcomes of patients undergoing an elective CND
in the presence of clinically positive jugular chain
nodes.
MATERIALS AND METHODS
This retrospective study is based on a review of the hospital and outpatient clinical records of the 464 patients who
underwent neck dissection for WDTCs in our institution
between 2000 and 2010. Of these, 51 (11%) patients who had
prior thyroidectomy without central or lateral neck dissection
had clinically positive jugular chain metastases (N1b1) without
Trivizki et al.: Elective Paratracheal Neck Dissection
evidence of central neck metastases (N1a2). All patients underwent preoperative central compartment evaluation by
ultrasound. The patients with clinical or radiological evidence
of neck metastases in level VI–VII (paratracheal and superior
mediastinum nodes) or thyroid bed were excluded.
Clinically positive nodes were defined as abnormal by
ultrasound. In all patients, clinically positive nodes were evaluated by fine-needle aspiration prior to surgery. All patients
underwent a standardized selective neck dissection involving
levels II–IV or II–V (LND) as described by the American Head
and Neck Society.2 Analysis of the data revealed that one surgeon routinely performed all the elective CND, whereas two
other surgeons routinely chose not to perform an elective procedure. The type of neck dissection was prespecified in all
patients before the operation. Elective CND was performed in
34 of 51 patients. One patient had bilateral jugular chain
metastases, and one patient had bilateral elective CND. The
follow-up interval ranged from 8 to 226 months, with a median
of 44 months.
None of the patients died of thyroid cancer. All patients
had postoperative treatment with radioactive iodine (I131). The
median ablative dose used was 150 mCi. An additional dose of
I131 (100–150 mCi) was given when any remaining uptake was
found 1 year after the first treatment. All patients received
postoperative hormone supplement (thyroxine), with a mean
dose of 1116 lg/week, aiming to keep a thyrotropin (TSH) level
of <0.1 mU/mL.
Total calcium serum levels were measured before and after
the operation. Follow-up included radioactive scanning 12
months after the initial I131 treatment and periodic neck ultrasound examinations. Thyroglobulin (TG), anti-TG antibody, and
TSH levels were monitored every 3 months. Twelve patients
(24%) had disease recurrence, and four (8%) of them had distant
metastases. The demographic and clinical data of the cohort
and its subgroups are listed in Table I.
Specimen dissection and tissue sampling were carried out
in accordance with the current guidelines for the histopathological assessment of head and neck cancer.3 The levels of neck
dissection specimens were identified, marked, and submitted for
pathological analysis. The lymph nodes were evaluated for
metastasis by pathologists specializing in head and neck cancer.
All identified nodes were submitted by the pathologist for further histological analysis. Lymph nodes were defined as
aggregates of encapsulated lymphoid tissue of any size that had
a peripheral sinus. Each lymph nodes was sectioned every
2 mm, put in different cassettes, and embedded in paraffin.
Sectioning was performed at 200 -lm intervals.
Clinical, demographic, and tumor variables were analyzed
using nonparametric qualitative and quantitative tests (JMP statistical software; SAS Institute Inc., Cary, NC). Fisher exact test
(StatCalc 2.0; University of Louisiana, Lafayette, LA) was used
when the number of events was <10. Two-tailed calculations
were performed in all statistical analyses. Disease-free survival
rate was calculated using the Kaplan-Meier method (JMP statistical software; SAS Institute Inc.). The study was approved by
the institutional review board committee (0112-11TLV).
RESULTS
The clinical and demographic characteristics of 51
patients who underwent 53 therapeutic selective neck
dissections of levels II–IV (n 5 48) or II–V (n 5 5) were
analyzed. Therapeutic LNDs without elective CNDs
were performed in 17 patients, and therapeutic LNDs
with elective CNDs were performed in 34 patients. The
main clinical and demographic characteristics of each
group are listed in Table I. All patients had undergone
Laryngoscope 123: June 2013
TABLE I.
Clinical and Demographic Characteristics of the Patients.
Variable
Lateral Neck
Dissection
Lateral and
Central Neck
Dissection
Entire cohort, n (%)
17 (33)
34 (67)
Age, mean 6 SD (range), yr
44 6 4
(18–70)
47 6 3
(17–77)
.7
.38
P
Sex, n (%)
Male
11 (65)
17 (50)
Female
6 (35)
17 (50)
1 (6)
1 (6)
1 (3)
1 (3)
.9
.9
16 (94)
1 (6)
33 (97)
1 (3)
.9
240 6 25
189 6 18
.11
1
2
10 (59)
0 (0)
15 (44)
2 (6)
.7
3
5 (29)
11 (32)
4a
4b
2 (12)
0 (0)
5 (15)
1 (3)
Primary tumor multifocality, n (%)
4 (24)
14 (41)
Primary tumor location, n
Isthmus
7
3
12
32
—
5 (29)
1
13 (38)
I
III
7 (41)
9 (53)
14 (41)
17 (50)
Iva
1 (6)
3 (9)
51 6 8
48 6 6
.81
24 (2–45)
22 (1–63)
.7
—
5 (2–17)
5 (29)
7 (21)
2 (12)
5 (15)
10 (59)
22 (64)
0
—
10 (29)
1
>2
—
—
6 (18)
18 (53)
<0.5
0.5–5
13 (76)
3 (18)
28 (82)
3 (9)
>5
1 (6)
3 (9)
1296 6 96
1025 6 68
Family history of PTC, n (%)
Irradiation exposure, n (%)
Neck dissection laterality, n (%)
Unilateral
Bilateral
Total of I131 treatments, n (%)
T stage at initial
presentation, n (%)
Lateral lobes
Upper pole
Primary tumor
extracapsular invasion, n (%)
.2
.2
.4
Overall TNM stage, n (%)
Follow-up time,
mean 6 SD (range), mo
Number of resected
nodes, median (range)
II–V
VI
Number of positive
nodes II–V, n (%)
0
1
>2
Number of positive
nodes VI, n (%)
.9
.7
—
Thyroid-stimulating
hormone, n (%), mU/mL
Thyroid hormone supplement,
mean 6 SD, lg
.6
.02
PTC 5 papillary thyroid carcinoma; SD 5 standard deviation.
Trivizki et al.: Elective Paratracheal Neck Dissection
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TABLE II.
Recurrence Rates.
Variable
Lateral Neck
Dissection, n (%)
TABLE III.
Thyroglobulin Level.
Lateral and
Central Neck
Dissection, n (%)
P
Recurrence site
Lateral Neck
Dissection
Lateral and
Central Neck
Dissection
P
Thyroglobulin level
Central neck
2 (12)
3 (9)
.73
<2.5 lg/mL, n (%)
12 (71)
29 (85)
.2
Lateral neck
Thyroid bed
6 (36)
1 (6)
2 (6)
0 (0)
.006
.15
>2.5 lg/mL, n (%)
Mean6SD, lg/mL
5 (29)
2.2 6 4.3
5 (15)
4.7 6 3
.63
Metastases
1 (6)
3 (9)
.71
Positive anti-Tg Ab, n (%)
1 (6)
2 (6)
1
Total*
6 (36)
6 (18)
.16
SD 5 standard deviation.
*Some patients had recurrence in multiple sites.
prior thyroidectomy, and there was no difference in the
age, gender, iodine treatment, initial tumor multifocality,
location or extra capsular invasion, total number of dissected nodes, TNM classification, stage, or TSH
suppression between the two groups (Table I). Thyroid
hormone supplement dosage was higher in the group
that did not have elective CND dissection (P 5 .02).
Twelve patients had disease recurrence; eight (67%)
were in the lateral neck, five (42%) were in the central
compartment region, and four (33%) were distant metastases. The overall recurrence rate was 18% (6/34) for the
group with elective CNDs compared with 35% (6/17) for
the group without elective CNDs (P 5 .16). Table II
shows the recurrence subsites in the two groups. The
rate of disease recurrence in the central neck compartment (level VI–VII) was 9% (n 5 3) in those undergoing
elective CNDs compared to 12% (n 5 2) in the group
without elective CNDs (P 5 .73). Figure 1 depicts the
Kaplan-Meier analyses of the two groups. The 5-year
disease-free survival rate of patients who had LND and
elective CND was 82% compared to 65% in those who
had LND alone. The difference in early disease-free survival between the two groups did not reach a level of
significance (P 5 .69).
We also evaluated the TG levels for both groups to
obtain objective data on postoperative recurrence.
The distribution of TG levels among patients who had
no evidence of recurrence were similar regardless of
whether or not an elective CND had been performed (Table III). Overall complication rate was 12% (6/51), and
two (33%) patients had RLN paralysis, three (50%) had
hypocalcemia, and one (17%) had bleeding that required
revision surgery (Table IV). The distribution of complication rates was similar regardless of whether or not an
elective CND had been performed (P 5 .3).
DISCUSSION
The generally accepted therapeutic management for
PTC with clinical evidence of nodal metastases is total
thyroidectomy and neck dissection, with the intent to
remove all of the involved lymphatic tissue. The type,
grade, site, and stage of the primary tumor determine
the risk of cervical metastases and therefore the form of
neck treatment.4 In head and neck squamous cell carcinoma, when the risk for positive neck nodes exceeds
20%, elective neck dissection is indicated not only for
treatment, but also for evaluation of the need for adjuvant therapy.5 However, because there is minimal
impact of neck metastases on survival of patients with
PTC, elective neck dissection is not routinely recommended in this population.6 Because of a lack of level 1
evidence, there is an ongoing debate on whether patients
with PTC should undergo elective neck dissection.4
Fig. 1. Kaplan-Meier analysis. The
graph shows the disease-free survival of patients undergoing therapeutic lateral neck dissection
(tLND), with elective central compartment neck dissection (eCND)
(black line) or without eCND (dotted
line). The 5-year disease-free survival rate was 82% in the group
with eCND and 65% in those without eCND (P 5 .69).
Laryngoscope 123: June 2013
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Trivizki et al.: Elective Paratracheal Neck Dissection
TABLE IV.
Complications.
Type of Complication
Lateral Neck
Dissection, n (%)
Lateral
and Central Neck
Dissection, n (%)
P
Permanent recurrent
laryngeal nerve paralysis
0 (0)
2 (6)
.19
Permanent hypocalcemia
Bleeding
1 (6)
0 (0)
2 (6)
1 (3)
.99
.62
Total
1 (6)
5 (15)
.33
Moreover, it is unknown whether patients who had prior
thyroidectomy undergoing therapeutic LND also require
an elective CND.7,8 Preoperative ultrasound can detect
nonpalpable nodal metastases in one-third of the
patients with PTC.9,10 An elective CND will detect occult
nodal metastases in 40% to 60% of the remaining
patients, and an elective LND will detect positive nodes
in 40%.11 Contralateral occult paratracheal nodes are
present in 10% to 25% of patients.12,13 Furthermore, the
risk of central compartment metastases is even higher
when there are jugular chain metastases.14 Hence, the
overall risk of occult nodal metastases in patients with
PTC is over 80%.11 Based on these numbers alone, some
surgeons recommended prophylactic CND (ipsilateral or
bilateral) in patients with PTC with clinically positive
jugular nodes.7 However, there is no level 1 evidence
showing a clinical advantage of elective CND in this
population. Another unanswered question is: Which population should undergo an elective CND (i.e., young
patients who have a high risk of nodal metastases or
older patients who have a low risk of neck metastases)?
Positive neck nodes in the former group have no impact
on survival, but they are associated with worse outcome
in the latter group.15,16 In addition, there is no consensus as to which type of elective neck dissection should be
performed, LND with a 40% risk of positive nodes in
level II–IV or CND with a 60% incidence of nodal metastases in level VI–VII. The answers to these questions
should be based on the potential benefit weighed against
the potential morbidity of the surgical outcome.
We assessed whether an elective CND offers an
advantage to patients with positive jugular chain metastases by investigating the early tumor-free survival,
recurrence rate, and complications. The clinical, demographic, and pathological variables were similar in the
groups with or without CND, and both groups also
received the same adjuvant radioiodine treatment dose
and had a similar degree of TSH suppression. Overall,
the difference in the disease-free survival (Kaplan-Meier
analysis) among the subgroups was not statistically
significant. The early recurrence rate in the central compartment was the same (9%–12%) in both groups. These
data are supported by TG levels that were identical in
both groups. The rate of neck metastases in the current
study was similar to that reported in the literature, and
as expected, the highest risk of recurrence was found in
the lateral neck.8,17 Taken together, these data demonstrate that prophylactic CND does not influence the
Laryngoscope 123: June 2013
early outcome of this population, and that the risk of
locoregional recurrence and distant metastases remains
similar whether or not CND was performed.8
Shah et al. evaluated the recurrence rates in
patients with well-differentiated thyroid carcinoma who
underwent a therapeutic LND, CND, or both and found
no differences in the rate of recurrence among the three
groups.8 The implications of their study and ours are
that although central compartment metastases are common in this population, they have minimal clinical
impact on the patient’s outcome.
The rationale for prophylactic CND is based on suspicion of a high incidence of occult nodal metastasis.
However, we found similar rates of nodal recurrence in
this area regardless of CNDs. One explanation for this
observation is that the adjuvant radioiodine treatment
efficiently cleared all microscopic residual cancer cells in
the central neck compartment.18 Another possibility is
that PTC cells survive but do not progress to clinically
evident disease in the metastatic environments, a phenomenon known as metastatic dormancy.19
Regarding complication, some will argue that there
is no increased risk in adding CND when performing
therapeutic LND. The incidence rates of hypoparathyroidism and vocal cord paralysis are well established and
not negligible following central compartment reoperation.20 Although the rates are acceptable given that
these patients are reoperated, in the presence of jugular
chain metastasis and no thyroid tissue, performing
elective CND puts the patient at increased risk for hypoparathyroidism and vocal cord paralysis.
We are aware of several limitations of our study. In
addition to its retrospective design, the small number of
patients in our cohort limits our ability to draw firm conclusions from the data. Although more than 14 items
were entered into our database, it is still difficult to
precisely delineate which factors influenced the risk of
tumor recurrence. Other parameters, such as the type
of radiologic evaluation during follow-up and the quality
of neck dissection, are difficult to quantify. These important variables can potentially affect the rate of
locoregional recurrence.
During the postoperative follow-up, the mean TG
levels were almost half among patients undergoing
elective CND compared to those not submitted to CND
(2.2 6 4.3 and 4.7 6 3 lg/mL, respectively). Although
this difference was not statistically significant (P 5 .63),
it is conceivable that our ability to distinguish between
small differences in TG level was limited by the sample
size. The retrospective nature of the study may also
have the potential of selection bias, because surgeons often tailor their treatment based on clinical node
involvement both preoperatively and intraoperatively.8
This does not apply to our study, however, because the
surgeons decide whether to perform CND in a regular
routine based on their preferences, regardless of clinical
or demographic parameters. We are aware that the follow-up of the patients in our cohort is relatively short.
Approximately 80% of all recurrences in PTC occur
within the first 5 years after initial treatment.21 Our
overall 5-year disease-free survival rate was 65% in
Trivizki et al.: Elective Paratracheal Neck Dissection
1567
patients undergoing LND alone and 82% in those undergoing LND and an elective CND. An identical 5-year
disease-specific survival rate was reported by the Toronto group on a similar group of patients.8 In their
study, the median length of follow-up was 104 months.
Although it is likely that our results represent a lower
estimation of overall recurrence rate, we believe that our
main finding—that elective CND does not change disease-free survival, will remain valid when an updated
evaluation of our data will be available in several years.
A final decision on the performance of an elective neck
dissection in PTC will have to wait for the availability of
level 1 evidence.
CONCLUSION
The current study shows for the first time that
neither the early tumor recurrence rate nor the diseasespecific survival is influenced by an elective central compartment neck dissection in patients with positive
jugular chain nodes. The absence of significant diseasefree survival advantage along with the known risk of
complications demonstrate the need for a prospective
evaluation of the common practice of this disease.
ACKNOWLEDGMENTS
The authors thank Esther Eshkol for editorial assistance.
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