Introduction
Patients with well-differentiated thyroid carcinomas
generally have favorable long-term outcomes. Papillary thyroid
carcinoma (PTC) is the most common thyroid carcinoma, representing
~80% of the newly diagnosed thyroid carcinomas (1). PTC has a relatively favorable
prognosis with a 10-year survival rate of 90–95%. Distant
metastases occur less frequently with PTCs compared with other
types of thyroid malignancy. When distant metastases are present,
the lungs and bones are the most frequently involved organs. By
contrast, brain metastases are rare, occurring in 0.1–5% of cases
(2). In the present study, we
treated 5 cases of PTC brain metastases in our institute and
retrospectively evaluated these patients.
Patients and methods
A retrospective database was generated from the
patient medical records of our institution for the years between
1976 and 2011. The patients were histologically diagnosed with PTC
and presented with a brain metastasis. The patients with brain
metastases that originated from a skull metastasis were
excluded.
Of the 5 patients that met our inclusion criteria
(Table I), 2 patients were men and
3 patients were women. The median age at diagnosis was 69 years,
while the average age was 64.6 years (range, 43–80 years). The
pathology of the primary thyroid disease was available for the 5
patients. The average lesion size was 53 mm in diameter (range,
20–110 mm). The average duration from PTC resection to the
detection of a brain metastasis on an magnetic resonance imaging
(MRI) or computed tomography (CT) scan was 91.7 months (range,
9.6–228.0 months). This study was approved by the Ethics Committee
for the University of Tsukuba.
 | Table ISummary of the 5 cases with papillary
thyroid cancer brain metastases. |
Table I
Summary of the 5 cases with papillary
thyroid cancer brain metastases.
| No. | Age (years) | Gender | Duration from T Ca
resection to brain meta (months) | No. of brain
meta | Lung meta or mediast
meta | Bone meta | Removal of brain
meta | External Irradiation
for brain meta | 131I
therapy | KPS before treatment
for brain meta | KPS after treatment
for brain meta | Outcome | Survival from brain
meta (months) | Cause of death |
|---|
| 1 | 69 | M | 84 | Sig | + | − | P | NP | NP | 50 | 60 | Dead | 9 | Mediast meta |
| 2 | 60 | M | 103 | Mul | + | + | P | SRS | P | 90 | 90 | Dead | 9 | Lung meta |
| 3 | 43 | F | 9.6 | Mul | − | + | P | NP | P | 70 | 100 | Dead | 11 | Hemorrhage from brain
meta |
| 4 | 71 | F | 34 | Mul | + | − | P | SRS | NP | 50 | 60 | Dead | 9 | Lung meta |
| 5 | 80 | F | 228 | Sig | + | + | NP | SRT | NP | 50 | 50 | Dead | 7 | Lung meta |
Results
Multiple brain metastases were observed in 3 of the
5 cases. Lung or mediastinal metastases were detected in 3 cases,
and bone metastases were observed in 3 cases. The patients were
treated with a varied combination of surgery, stereotactic
radiosurgery (SRS), stereotactic radiotherapy (SRT) and
131I therapy. Four patients underwent surgery for brain
metastases, resulting in a gross total removal (GTR) in 1 patient
with a single metastasis. With regards to radiation treatment, 2
patients received SRS and 1 patient underwent SRT. Two patients
received 131I therapy.
The median Karnofsky performance scores (KPSs) prior
and subsequent to the treatments for the brain metastases were 50%
(range, 50–90%) and 60% (range, 50–100%), respectively. The
patients were deceased at the last follow-up. The mean overall
survival following the diagnosis of brain metastases was 9.0±1.414
months (± SD; range, 7–11 months). One patient succumbed to an
intratumoral hemorrhage of the metastatic brain tumor, while 3
patients died as a result of lung or mediastinal metastasis
progression.
Discussion
In this retrospective study, the patients diagnosed
with PTC brain metastases had an average overall survival of 9.0
months. This survival time is shorter compared with the average
overall survival of patients with brain metastases from other
thyroid cancers, which has been previously reported to be 4.7–29.2
months (3–8). Chiu et al(4) reported that the overall median
survival of patients with brain metastases from well-differentiated
thyroid cancers was 12.4 months (4.7 months for patients with
metastasis from whole thyroid cancer, comprising 11 anaplastic, 32
differentiated and 4 medullary cancers). Of the patients with known
causes of death, only 22.2% of the deaths were attributable to
brain metastases (7). Our present
data regarding the causes of death are similar to the
abovementioned data. However, our findings have shown that the
prognosis of the 5 patients in this study was worse compared with
that in previously published studies (5,6,8,11),
with the exception of one study (5) that included a high percentage of
anaplastic cases. As shown in Table
II, PTC patients who present with other organ metastases have a
shorter survival period following the diagnosis of a PTC brain
metastasis. Results of the present study may have demonstrated a
poorer outcome as our series comprises patients with other organ
metastases, particularly metastases to organs of the respiratory
system, such as the lung or mediastinum, which might indicate a
progressed or advanced disease state. Although most brain
metastases were locally controlled, it is hypothesized that other
advanced organ metastases or systemic diseases may have caused the
death of PTC patients with controlled brain metastases.
| Table IIPrevious studies regarding thyroid
cancer brain metastasis. |
Table II
Previous studies regarding thyroid
cancer brain metastasis.
| Author (Refs.) | Year | No. of T Ca | Meta in all T Ca
without brain meta | Survival from brain
meta (months) | Death due to brain
meta | No. of papillary T
Ca | Meta in papillary T
Ca without brain meta | Survival in papillary
T Ca from brain meta (months) |
|---|
| Biswal et
al(11) | 1994 | 5 | 4 | 27.4 | 0 | 1 | 1 | 6.0 |
| Hjiyiannakis et
al(1) | 1996 | 6 | 6 | 7.8 | 3 | 6 | 6 | 7.8 |
| Salvati et
al(8) | 2001 | 12 | 8 | 19.8 | 2 | 3 | 2 | 35.3 |
| McWilliams et
al(6) | 2003 | 16 | 3 | 17.4 | 2 | 10 | 1 | 23.6 |
| Kim et
al(5) | 2009 | 9 | 7 | 29.2 | 1 | 7 | 6 | 31.0 |
| Present study | 2012 | 5 | 5 | 9.0 | 1 | 5 | 5 | 9.0 |
Although there is no clearly defined protocol for
the management of intracranial metastases from thyroid cancer
(9), surgery is generally
considered to be the best therapeutic choice for prolonged survival
and regression of neurological symptoms (2,3,5,7,9,10).
In previous studies, patients undergoing SRS had an overall median
survival time of 33–37.4 months (8,11),
with GTR being an attractive option for the local control of a
solitary or few lesions (9).
Hjiyiannakis et al(1) noted
an apparent benefit of radioactive iodine treatment when uptake
scans in the brain were positive, although uptake by cranial
metastases is relatively infrequent and has been reported to occur
in only 23–25% of cases (7).
However, McWilliams et al(6) found no evidence to support the use of
chemotherapy in patients with brain metastasis from thyroid
carcinoma as it was not utilized in any of the studies mentioned
previously and no responses were reported in their study cohort. In
the present study, the 5 patients who underwent surgery and/or
external irradiation therapy had poor prognoses. This result
suggested that these therapeutic options did not improve the
survival of patients with PTC brain metastases due to systemic
advanced disease, but provided good local control of the metastatic
brain tumor.
It is generally accepted that patients with
metastases from a primary well-differentiated thyroid carcinoma
have a favorable prognosis. However, PTC brain metastases should be
considered a terminal clinical symptom in PTC and most patients
with brain metastases also succumbed to the disease due to the
development of metastases to the fetal organs rather than brain, as
well as organs of the respiratory system. Therefore, it is
important to identify the general condition of the patient and
consider the expected prognosis prior to the planning of
therapeutic schedules.
Acknowledgements
This study was partly supported by a Grant-in-Aid
for Scientific Research (C), no. 23592085, from the Ministry of
Education, Culture, Sports, Science and Technology-Japan
(MEXT).
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