PhiliPPine Journal of otolaryngology-head and neck Surgery Vol. 35 no. 1 January – June 2020 PhiliPPine Journal of otolaryngology-head and neck Surgery Vol. 35 no. 1 January – June 2020

PhiliPPine Journal of otolaryngology-head and neck Surgery 4746 PhiliPPine Journal of otolaryngology-head and neck Surgery

ORIGINAL ARTICLES

Philipp J Otolaryngol Head Neck Surg 2020; 35 (1): 46-50 c Philippine Society of Otolaryngology – Head and Neck Surgery, Inc.

Prognostic Value of Thyroidectomy and
Tracheostomy in Anaplastic Thyroid Carcinoma

Carlo Victorio L. Garcia, MD
Arsenio Claro A. Cabungcal, MD
Alfredo Quintin Y. Pontejos, Jr., MD

Department of Otorhinolaryngology
Philippine General Hospital
University of the Philippines Manila

Correspondence: Dr. Arsenio Claro A. Cabungcal
Ward 10, Department of Otorhinolaryngology
Philippine General Hospital, Taft Ave., Manila 1000
Philippines
Phone: (632) 8554 8400 local 2152
Email: aacabungcal@up.edu.ph (email address may be
published)

The authors declared that this represents original material
that is not being considered for publication or has not been
published or accepted for publication elsewhere in full or in
part, in print or electronic media; that the requirements for
authorship have been met by all the authors, and that each
author believes that the manuscript represents honest work.

Disclosures: The authors signed a disclosure that there are no
financial or other (including personal) relationships, intellectual
passion, political or religious beliefs, and institutional
affiliations that might lead to a conflict of interest.

Presented at the 4th European Otolaryngology-ENT Surgery
Conference, August 15-17, 2019, Rome, Italy.

Presented at the Philippine Society of Otolaryngology Head
and Neck Surgery Descriptive Research Contest. December 6,
2019. Palawan Ballroom, Edsa Shangri La Hotel, Mandaluyong
City.

ABSTRACT
Objective: To determine the prognostic value of surgical interventions done among patients
with anaplastic thyroid carcinoma (ATC)

Methods: A five-year retrospective chart review of 25 patients was done and baseline
characteristics determined. Patients discharged alive as of the time of last chart entry were
followed up by phone interview or personal visit. Overall survival was the main outcome measure
which was plotted as Kaplan-Meier estimates and compared via log-rank test. The incidence of
complications surrounding tracheostomy and thyroidectomy were also noted.

Methods:
Design: Ambispective Cohort Study
Setting: Tertiary National University Hospital
Participants: All private and public (charity) patients seen at the wards or clinics

diagnosed with ATC via fine needle cytology or tissue histopathology.

Results: All patients presented with either stage IV-B or stage IV-C disease. A significant difference
in survival curves was noted when comparing between the two stages (p<.05). Subgroup
analysis per stage revealed no significant difference in overall survival when comparing patients
who did not undergo surgery, those who underwent tracheostomy or those who underwent
thyroidectomy for both IV-B (p=.244) or IV-C (p=.165) disease. The incidence of complications
for tracheostomy was 60%, the most common being mucus plugging. For thyroidectomy, the
incidence of complications was 80% with hypocalcemia being the most common.

Conclusion: The current available data fails to demonstrate any significant survival advantage of
tracheostomy or thyroidectomy when performed among similarly staged patients.

Keywords: anaplastic thyroid cancer; thyroidectomy; tracheostomy; survival

Creative Commons (CC BY-NC-ND 4.0)
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Of all the known malignancies, anaplastic thyroid carcinoma
(ATC) carries one of the worst prognosis with a 5-year survival rate of
only 5.6-11.4% and a median life expectancy of only 2-12 months.1-5
The incidence of ATC is pegged at 1 to 2 cases per million people.2
Despite being the least common thyroid malignancy, it accounts for
roughly 50% of all thyroid cancer deaths.6 All anaplastic cancers are
automatically stage IV upon diagnosis: IV-A is disease limited to the
thyroid, IV-B is tumor invading through thyroid capsule and/or regional
metastasis and IV-C involves distant metastasis. At least 90% of patients
with ATC are elderly (>60 years) at presentation.7,8 Because of this, and
the advanced disease at presentation, surgical efforts at complete
resection remain controversial as they are associated with significant
morbidity and reduced quality of life. In our institution, most of these
patients are treated with palliative rather than curative intent with most
of the procedures geared towards relief of airway obstruction. Recently
however, cohort studies with sizeable patient pools in Italy and Korea
have shown significant survival benefit for curative resection when
performed among appropriately selected patients.9,10

A search of local literature via MEDLINE (PubMed) and HERDIN
only yielded two descriptive studies on ATC among Filipinos. Sunga
et al. performed a retrospective study of 17 patients from 1973-1994
and compared the outcomes of thyroidectomy and radiotherapy in
resectable ATC versus tracheostomy and radiotherapy in unresectable
ATC.11 Although they determined that combined thyroidectomy
and radiotherapy resulted in a longer mean survival, this was not
analyzed with respect to staging.11 A more recent study by Lo et al.
detailed the symptomatology, demographics and clinical course of
these patients. However, it did not describe the survival benefit of
surgical interventions done on these patients nor did it mention the
complications or morbidities surrounding these procedures.12

Considering recent evidence that refocuses our attention on surgery
as the primary modality for curative efforts, we aim to validate if this
was applicable at the local setting as well. This study aims to determine
the prognostic value of surgical interventions done among patients
with anaplastic thyroid carcinoma (ATC) in our institution.

METHODS
With Institutional Review Board approval, this ambispective

cohort study was conducted among all patients with cytologically or
histopathologically confirmed anaplastic thyroid carcinoma admitted
at the in-patient ward or seen at the out-patient clinic of the Department
of Otorhinolaryngology of the Philippine General Hospital from
January 2013 to January 2018. Securing informed consent was waived
for patients who expired while admitted and whose death certificate
was already available in the records. For patients who were discharged

alive but died sometime after, informed consent was obtained from the
nearest kin.

All the inpatient and outpatient charts of patients with either
initial cytopathologic diagnosis of ATC via fine needle biopsy and/
or final histopathologic confirmation of ATC within the study period
were reviewed. Excluded were patients with an initial diagnosis of ATC
refuted by subsequent histopathological examination.

Patient demographics and baseline characteristics were obtained
from the selected charts. Patients were further classified into one of 3
groups: 1) no surgical intervention, 2) tracheostomy with or without
debulking, 3) total thyroidectomy/wide excision of tumor with or
without neck dissection. The rates of intraoperative and postoperative
complications were determined for each surgical intervention done.

Disease-specific mortality was the primary endpoint. If the chart
reflected that the patient was discharged alive as of the time of last
admission/consult, the current status was verified by a recorded phone
call to the contact person identified in the records or a personal visit
at the listed address. Information gathered was limited to the date of
death (if applicable) and cause of death (if applicable). If the patient
or contact person was not reachable through listed channels (through
phone or personal visit at listed address), they were censored in the
final analysis.

Kaplan-Meier disease-specific survival curves were generated
comparing each stage followed by subgroup analysis per stage of the
different interventions the patients received. Survival estimates were
compared via log-rank test using SPSS 17 (SPSS Inc., Chicago IL).

RESULTS
A total of 25 patients had charts available for review for the time

period covered. There was a 3:1 female to male preponderance and a
median age of presentation of 59 years old (range of 44 to 87 years old).
The baseline characteristics and the surgical interventions performed
for each patient are summarized in Table 1.

The primary outcome was determined in only 13 of the 25 patients.
The rest were censored as of the time of last chart entry or clinic visit.

The top causes of death among stage IV-B patients were sepsis/
respiratory failure from pneumonia, arrhythmia from myocardial
infarction and upper airway obstruction. The top causes of death
among stage IV-C patients were sepsis from pneumonia and multiorgan
dysfunction from tumor metastasis. The mean overall survival of stage
IV-B patients was 5 weeks while that of IV-C patients was only 2 weeks.
Figure 1 shows the Kaplan-Meier curves grouped according to stage. As
expected, log-rank test showed that the survival probability of stage
IV-B patients was significantly different from IV-C patients (p value =.01).

Figures 2 and 3 show a subgroup analysis per stage and compared

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the various surgical interventions done on these patients. Comparing
same stage patients, the data shows that neither tracheostomy nor
thyroidectomy significantly altered the survival of patients compared
to those who did not undergo any surgical intervention (p value = .21
for IV-B, p value = .17 for IVC).

Thyroidectomies were associated with postoperative hypocalcemia
40% of the time. Tracheostomies were associated with complications
62% of the time and the most common was mucus plugging. Other
tracheostomy complications included tube infiltration by tumor,
surgical site infections and bleeding per stoma.

DISCUSSION
This study corroborates the previous findings of Lo et al. that

demonstrated similar symptomatology among their cohort of
patients.12 Aside from a rapidly enlarging neck mass, dysphagia was
the next most common complaint, occurring in 72% of patients.

Table 1. Clinical characteristics of 25 ATC patients and enumeration of surgical interventions
performed per stage

Factors Cases (n=25)

Gender

Female

Age

<60 years

≥60 years

Number of symptomatic months prior to diagnosis

<1 month

1-3 months

>3 months

Nodal metastasis

Yes

Resectability of primary tumor

Yes

Equivocal

Stage

IV-B

IV-C

IV-B IV-C
Surgical intervention
None 3 2
Tracheostomy (with or without debulking) 8 7
Thyroidectomy (with or without neck dissection) 4 1

Figure 1. Kaplan-Meier curves showing the effect of staging on overall survival

Figure 2. Kaplan-Meier curves showing effect of surgical interventions on overall
survival of stage IVB patients

Figure 3. Kaplan-Meier curves showing effect of surgical interventions on overall
survival of stage IVC patients

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In our cohort, dyspnea was also a common complaint (68%) followed
by hoarseness (64%). Lateral neck node (levels II-IV) involvement was
observed in 60% of patients. Involvement of the central nodal basin
was more difficult to determine due to confluence with the anterior
neck mass.

Distant metastasis was most commonly found in the lungs which
presented as multiple nodules/masses (“cannonball” lesions) readily
apparent on chest radiography or computed tomography. Pulmonary
metastasis contributed to prolonged mechanical ventilation and
significant respiratory difficulty, even post-tracheostomy. Bony and
hepatic metastasis was also apparent in 30% and 10% of patients,
respectively.

There is little debate that ATC confined within the thyroid gland
(Stage IV-A) is best treated with total thyroidectomy but unfortunately,
none of our patients were staged IV-A on diagnosis. The treatment
of IV-B disease is more controversial. Several studies have identified
prognostic factors that predict the success of surgical resection: age<60-
70 years, tumor within thyroid capsule and absence of leukocytosis.13,14
As seen in our cohort, patients rarely fulfilled these prognostic criteria.
Half of our cohort presented in the elderly (>60-year-old) population.
They had sizeable primaries which grew rapidly, sometimes in as fast
as two weeks. These factors underscore the need for surveillance and
expeditious workup of any rapidly enlarging neck mass or sudden
enlargement of previous goiter.

There is an emerging body of evidence that surgery still confers
longer cumulative survival even in patients with negative prognostic
factors given that the longest survivors had surgical resection as part
of their treatment.15,16 In our cohort, tumor resectability was defined
as any tumor without 270 degree encasement of the common carotid
artery or prevertebral fascia extension. This definition is based on
the 2002 American Joint Committee on Cancer definition for a T4b
tumor which was the convention for determining resectability.17 For
patients with IV-B disease, tumor was already deemed unresectable
in a third of cases. Despite having theoretically resectable tumors in
7 patients, thyroidectomy was only performed in four patients. Two
of them also underwent therapeutic bilateral neck dissection for N1b
disease. Although there were no serious intraoperative morbidities,
postoperative hypocalcemia was a common occurrence.

Patients who underwent resection continue to have survival curves
similar to patients treated with palliative tracheostomy or those who
did not undergo any surgical intervention. A probable reason for
this is the difficulty in achieving R0 or even R1 margins. The National
Comprehensive Cancer Network thyroid cancer guidelines even
mention that R0/R1 resection is achieved usually incidentally for
thyroidectomies for other causes.18 The difficulty in achieving clear

margins puts patients at risk for early recurrence and distant tumor
dissemination. Although external beam radiotherapy is a viable
treatment for tumor residuals, its effectivity is still unassessed in our
setting as patients rarely initiate treatment either due to preference
or limitation of funds. In our cohort, all patients who underwent total
thyroidectomy were unable to initiate radiotherapy treatment.

Thyroidectomies were rarely performed among IV-C patients due
to their poor health status at presentation and the dismal prognosis.
In our series, only one patient with metastatic disease underwent
thyroidectomy. Most only consented to palliative airway management
with tracheostomy. Like the IV-B subgroup, surgical interventions do
not seem to significantly improve overall survival in IV-C patients.

Airway obstruction in ATC can be due to extrinsic compression by
tumor, direct laryngotracheal invasion or vocal cord paralysis. Stridor
occurs in 20-30% of patients and the degree of obstruction may worsen
during the patient’s clinical course i.e. during radiotherapy, upon
endotracheal manipulation, or onset of pulmonary infection.19

The latest American Thyroid Association 2015 guidelines advised
against prophylactic tracheostomy in non-obstructed patients due
to the significant reduction in their quality of life.20 In our institution,
we often do it prophylactically due to the rapidly progressive nature
of the disease and concern for lack of airway specialists in their home
area. However, it is not a procedure without risk, as tracheostomy can
pose unique challenges when done in this population, both in the
intraoperative and postoperative settings. In most instances, the size of
the tumor precludes easy exposure of the trachea and the airway may
be considerably displaced by the mass. Prior computed tomographic
evaluation is highly recommended to guide the surgeon as to the
route of access. The tumor can be debulked to expose the trachea
underneath and we routinely send tissue samples for histopathological
confirmation of disease. This procedure is ideally done in the operating
room and never at bedside. In this cohort, only one patient succumbed
to acute upper airway obstruction when endotracheal intubation and
emergent tracheostomy failed to secure a patent airway.

The postoperative course of these tracheostomized patients can
also be troubling. In our cohort, 40% of patients experienced recurrent
bouts of mucus plugging refractory to routine nursing care which
necessitated multiple referrals to the attending otolaryngologist. The
occurrence of this complication is due to the design of the tracheostomy
tube we use for these patients. We favor an extended tube with a neck
flange that can be adjusted anywhere along the length of the tube
(TRACOE® vario, REF 451 TRACOE medical GmbH, Nieder-Olm, Germany).
This bidirectionality affords the surgeon greater flexibility: proximal
extension for anterior neck bulk and distal extension for intraluminal
tracheal involvement. The trade-off is the absence of an inner cannula

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that makes the management of tracheal secretions more problematic.
Furthermore, peristomal bleeding and direct intraluminal extension of
the tumor are frequent occurrences that can contribute to intermittent
periods of airway obstruction and hypoxemia. All these factors pose
significant risks and raise the question whether routine stomal nursing
care can be safely done at home.

Our study has several limitations. The primary outcome of disease-
specific mortality, was only reliably determined in 52% of patients
despite extensive efforts to track patients and determine their status.
Better follow-up and patient tracking can lead to more reliable data
which may translate to more robust conclusions. Another limitation
was that we were only able to ascertain postoperative complications
from inpatient records. It is highly probable that patients may have
suffered other postoperative complications after discharge such as
tube displacement/obstruction. Future research should investigate the
prognostic value of other interventions such as chemotherapy and/or
radiotherapy rendered to patients who did not undergo any surgery.

Currently, we can conclude that the data at hand is insufficient
to affirm that tracheostomy or thyroidectomy significantly alter the
survival of similarly staged patients. These findings caution us surgeons
to be more pragmatic in offering interventions to these patients. They
must be advised about the proven benefits and risks surrounding the
procedure. Supportive care without surgery is an acceptable alternative
if the patient so desires. Ultimately, it is about enabling patients to
make informed decisions regarding their care, especially since current
treatment efforts continue to be disappointing and the prognosis
continues to be grim.