Evidence from an updated meta-analysis of the prognostic impacts of postoperative radiotherapy and chemotherapy in patients with anaplastic thyroid carcinoma
OncoTargets and Therapy
evidence from an updated meta-analysis of the prognostic impacts of postoperative radiotherapy and chemotherapy in patients with anaplastic thyroid carcinoma
Quansong Xia 2
Wei Wang 1
Juan Xu 0
Zhaoming Zhong 1
0 Department of internal Medicine, The People's hospital of guandu District , Kunming, People's republic of china
1 Department of h ead and n eck s urgery, The Third a ffiliated h ospital of Kunming Medical University
2 Department of clinical laboratory
PowerdbyTCPDF(ww.tcpdf.org) Xue chen 2 chuanzheng sun 2 Background: Radiotherapy and chemotherapy are the two important postoperative management approaches for anaplastic thyroid carcinoma (ATC), and several studies have suggested that postoperative radiotherapy and chemotherapy can prolong the survival of patients with ATC. However, the results remain inconsistent. Objective: A meta-analysis was performed to address whether postoperative radiotherapy and chemotherapy could prolong the survival of patients with ATC. Methods: Relevant studies were included, and pooled hazard ratios (HRs) together with 95% confidence intervals (CIs) were calculated. Results: Ten relevant studies on factors that affect the prognosis for ATC were included in this meta-analysis, evaluating a total of 1,163 patients. The pooled HR for overall survival (OS) was calculated using a random-effects model. The pooled results demonstrated that for all patients with resectable ATC, the combination of surgery and radiotherapy significantly reduced the risk of death compared with surgery alone (HR =0.51, 95% CI: 0.36-0.73, Z=3.66, P=0.0002). To investigate the prognostic impacts of chemotherapy in patients with ATC, we also calculated the pooled HR of chemotherapy for OS using a random-effects model; however, the pooled results suggested that chemotherapy did not prolong the survival of ATC patients compared with controls (HR =0.63, 95% CI: 0.33-1.21, Z=1.39, P=0.17). Conclusion: This study provided evidence that currently, for patients with ATC, postoperative radiotherapy may prolong survival; in contrast, chemotherapy did not improve long-term survival. meta-analysis Thyroid cancers include papillary, follicular, medullary, and anaplastic carcinomas. cancers,1-5 ATC is responsible for 14%-50% of all thyroid carcinoma-related deaths.6-9 Thus, ATC is a special type of thyroid cancer with high degree of malignancy and poor prognosis. Patients with ATC are typically in their sixth or seventh decade of life. This disease is usually characterized by aggressive growth features and frequently causes extensive local invasion and distant metastases. Therefore, the management of patients with ATC is extremely difficult, and there is little consensus regarding a standard successful treatment protocol.10,11 During the past few years, some studies
anaplastic thyroid carcinoma; postoperative radiotherapy; chemotherapy; prognosis
open access to scientific and medical research
O r i g i n a l r e s e a r c h
*These authors contributed equally
to this work
Although anaplastic thyroid carcinoma (ATC) accounts for only 2%–5% of all thyroid
have demonstrated that multidisciplinary treatment plays
an important role for patients with ATC and that
postoperative radiotherapy is the main treatment approach rather than
chemotherapy.12–14 However, it remains uncertain whether
this multimodal treatment truly improves survival because
most studies have a small sample size and poor statistical
power due to the relatively low incidence of ATC.
Previously, we reported that radiotherapy combined
with surgery appears to increase overall treatment efficacy
for ATC patients and prolong survival; in contrast,
chemotherapy was ineffective.15 However, other studies have
reported conflicting results.16–18 Therefore, the objective of
this study was to perform a meta-analysis to address whether
chemotherapy and radiotherapy could prolong the survival
of patients with ATC.
.dow lsue Web of Science, VIP Database for Chinese Technical
/w no Periodicals, Wanfang Data Knowledge Service Platform,
ttp pe and China National Knowledge Infrastructure (CNKI) for
h ro articles published up to April 2017, using the terms ATC and
frodm F anaplastic thyroid carcinoma. A database was then created,
aed with no limits established with respect to language or study
lnow design. Studies included in this meta-analysis were required
yod to be 1) original studies and 2) studies reporting hazard ratios
raep (HRs) with 95% confidence intervals (CIs) or sufficient data
hdT to calculate HRs and 95% CIs. All studies were independently
trsngea vmeertiafi-eadnaalgyasiinssbtythtwe oininclvuessitoignaatonrds.eTxchleufsiirosntacurtihteorri,apfuobrlitchai-s
oaT tion year, country, language, sample size for ATC patients,
cnO and reported HR(s) were extracted from each included study.
These processes were performed independently by two
investigators (WW and QX), and a consensus was reached.
Pooled HRs and 95% CIs were calculated.19 In addition,
χ2-based Q statistics and I2 metrics were used to assess the
heterogeneity between studies. When I2<50%, a fixed-effects
model was used to calculate pooled HR; otherwise, a
randomeffects model was used for this purpose. The prognostic
impacts of chemotherapy and postoperative radiotherapy in
ATC patients were assessed by meta-analysis. All
statistical analyses were performed using the Review Manager
software (v.5.2; The Nordic Cochrane Centre, The Cochrane
Collaboration, Copenhagen, Denmark) and STATA (v. 12.0;
StataCorp LP, College Station, TX, USA).
A database that included each article’s first author,
publication year, country, language, sample size, and other
important information was established based on the information
extracted from 10 relevant studies15–18,20–25 that satisfied the
inclusion criteria (Table 1). The original search yielded
a total of 2,563 articles related to the keywords. Figure 1
summarizes the selection process of this study. After titles,
keywords, and abstracts were screened, 2,478 of these
articles were excluded. The full texts of 85 articles were
reviewed, and an additional 75 articles were excluded (with
74 articles excluded for not providing usable data and one
article excluded due to the duplication of the same article
in different languages); thus, 10 studies (a total of 1,163
patients) remained for further review.
The pooled HR for overall survival (OS) was calculated
using a random-effects model. The pooled results
demonstrated that for all patients with resected ATC, the
combination of surgery and radiotherapy significantly reduced
the risk of death compared with surgery alone (HR =0.51,
95% CI: 0.36–0.73, Z=3.66, P=0.0002) (Figure 2). In
addition, to investigate the prognostic impact of chemotherapy
in ATC patients, we calculated the pooled HR of
chemotherapy for OS using a random-effects model; however, the
pooled results demonstrated that ATC patients treated with
chemotherapy did not exhibit prolonged survival relative to
patients who did not receive chemotherapy (HR =0.63, 95%
CI: 0.33–1.21, Z=1.39, P=0.17) (Figure 3).
To assess the stability of our results, a sensitivity analysis
was performed by removing one study at a time. The pooled
HR for patients who received a combination of surgery and
radiotherapy or chemotherapy compared with control patients
was not significantly changed, suggesting that our results
were stable. Funnel plots for this meta-analysis were
symmetric (Figure 4), indicating the absence of publication bias.
Finally, we used STATA software to perform Egger’s test to
calculate publication bias. No publication bias was detected
via Egger’s test, which was performed to provide statistical
evidence for funnel plot symmetry (P=0.183 for surgery
combined with radiotherapy; P=0.441 for chemotherapy).
ATC is one of the most aggressive types of malignant tumor
in humans,26 and the prognosis of patients with ATC is
extremely poor; in particular, only 20% of affected patients
survive for 1 year, and the median survival duration is
3–9 months after diagnosis.1–5,11,27 There is currently no
standardized therapeutic regimen for ATC patients. Multimodal
OncoTargets and Therapy 2018:11
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therapy has been reported to achieve better results than
unimodal treatment;12–14 however, no firm conclusions have been
reached and no individualized treatment regimens have been
established.10,11 Although most studies have demonstrated
that postoperative radiotherapy can prolong the survival
of ATC patients while chemotherapy is ineffective for this
purpose, it remains unclear which treatment truly improves
survival because most studies have a small sample size and
poor statistical power due to the relatively low incidence of
ATC. In this study, we performed a meta-analysis to address
whether postoperative radiotherapy or chemotherapy could
prolong the survival of ATC patients and attempted to
determine the best treatment strategy to guide therapeutic
Our pooled results demonstrated that for all patients
with resectable ATC, the combination of surgery and
postoperative radiotherapy significantly reduced the risk
of death compared with surgery alone; in contrast,
chemotherapy did not prolong the survival of ATC patients. In fact,
American Thyroid Association (ATA) guidelines already
recommend that definitive radiotherapy should be offered
after complete or near complete surgical resection (R0/R1)
in patients without metastatic disease.28 In addition, it has
been suggested that for patients whose performance statuses
permit such treatment, multimodal regimens that include
chemotherapy result in the longest median survival.5,11,29,30
The aforementioned findings raise the following question:
if surgery followed by radiotherapy and chemotherapy
truly improves the long-term survival of ATC patients,
why would prior studies have reported differing curative
effects for this therapeutic approach?17,20,22,25 To address this
question, we performed a literature review; based on this
review, we considered the following potential explanations
for differences in reported curative effects. First, there is no
standard protocol for either chemotherapy or radiotherapy
for ATC, and these treatments cannot be continued because
rapid enlargement occurs, particularly in elderly patients.31
Second, for radiotherapy, the dose appears to be important;
several studies have demonstrated a clear improvement in
survival among patients given higher doses of radiotherapy.32
Furthermore, there is currently no general consensus
regarding which chemotherapy regimens are best, although several
studies have compared different agents and demonstrated
that toxic regimens are poorly tolerated.5,11,33,34 Although the
pooled result in our study suggested that chemotherapy is
ineffective, we still cannot completely exclude its potential
for producing beneficial effects.
In contrast, several limitations of the current meta-analysis
should be noted. First, despite our best attempts to gather
evidence from the literature, we were unable to perform a
methodological assessment of certain studies due to a lack
of usable data. Additional work must be performed in the
future. Second, there is potential publication bias in this study
because we did not consider several unpublished articles and
abstracts because these unpublished works were not
available. In addition, our meta-analysis only included studies
published in English or Chinese, with other publications
excluded due to our language criteria; this restriction may
also have introduced bias and affected our findings. Finally,
our meta-analysis may have been too underpowered to
acquire original data from the included studies. Despite all of
the aforementioned limitations, this study provided evidence
that for ATC patients, surgery combined with radiotherapy
may offer prolonged survival; in contrast, postoperative
chemotherapy did not improve long-term survival.
This study provided evidence that surgery combined with
radiotherapy may prolong survival in ATC patients; in
contrast, postoperative chemotherapy did not improve long-term
This work was supported by the National Natural Science
Foundation of China (81560470 and 81773127) and the
Special Foundation of Young and Middle-aged Academic
Leaders Reserve Talent in Yunnan Province (2015HB086).
The authors report no conflicts of interest in this work.
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