Chenyuan Li1,2, Qi Wu1,2, Shengrong Sun1. 1. Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China. 2. Authors contributed equally to this article.
Abstract
Distant metastasis (DM) is the dominant negative prognosis for thyroid carcinoma. Radioactive iodine (RAI) therapy serves as an effective treatment for thyroid carcinoma. However, resistance to RAI occurs in patients with DMs. The present study aims to discriminate patients who may benefit from RAI. We extracted patients with thyroid cancer in the Surveillance, Epidemiology, and End Results program and analyzed thyroid cancer-specific survival after radiotherapy based on age and grade subgroups. A total of 1608 patients having DMs were eligible, including 521 (32.4%) cases with bone metastasis, 90 (5.6%) cases with brain metastasis, 158 (9.8%) cases with liver metastasis, 995 (61.9%) cases with lung metastasis, and 50 (3.1%) cases with other metastases. Advanced age, poor differentiation, follicular carcinoma, lymphatic metastasis, tumor size >10 mm, and extracapsular invasion are associated with pulmonary metastases. With respect to patients with DM, RAI therapy improved the survival in the age <45 years group and the well-/moderately differentiated group. For patients with pulmonary metastasis, RAI improved the survival in the higher grade group but did not have a strong effect in the better grade group. Our data indicate that the disparity of metastatic sites has different risk factors. Similarly, this finding indicates that RAI should be precisely applied to patients who undergo DM but are young and have well-/moderately differentiated tumors and may improve survival in pulmonary metastasis patients with poor grade tumors.
Distant metastasis (DM) is the dominant negative prognosis for thyroid carcinoma. Radioactive iodine (RAI) therapy serves as an effective treatment for thyroid carcinoma. However, resistance to RAI occurs in patients with DMs. The present study aims to discriminate patients who may benefit from RAI. We extracted patients with thyroid cancer in the Surveillance, Epidemiology, and End Results program and analyzed thyroid cancer-specific survival after radiotherapy based on age and grade subgroups. A total of 1608 patients having DMs were eligible, including 521 (32.4%) cases with bone metastasis, 90 (5.6%) cases with brain metastasis, 158 (9.8%) cases with liver metastasis, 995 (61.9%) cases with lung metastasis, and 50 (3.1%) cases with other metastases. Advanced age, poor differentiation, follicular carcinoma, lymphatic metastasis, tumor size >10 mm, and extracapsular invasion are associated with pulmonary metastases. With respect to patients with DM, RAI therapy improved the survival in the age <45 years group and the well-/moderately differentiated group. For patients with pulmonary metastasis, RAI improved the survival in the higher grade group but did not have a strong effect in the better grade group. Our data indicate that the disparity of metastatic sites has different risk factors. Similarly, this finding indicates that RAI should be precisely applied to patients who undergo DM but are young and have well-/moderately differentiated tumors and may improve survival in pulmonary metastasispatients with poor grade tumors.
Entities:
Keywords:
EBRT; RAI; distant metastases; pulmonary metastases; thyroid cancer
Thyroid cancer (TC) is the most common endocrine neoplasm but has a relatively good
prognosis, exhibiting incidence rates of 3.1% and death rates of 0.7%.[1] Distant metastases (DMs) from TC were rare and were only diagnosed in 1% to
4% of patients. However, the outcome of these patients was poor, which was the
leading cause of TC-related death.[2] Given the potential impact of all available treatment strategies, precise
assessment at the time of diagnosis is a pivotal element of clinic decision-making
regarding the timing and type of initial therapy, including local therapy or
systemic treatment.Generally, the most common site of metastases is the lung.[3] Metastasis to the lung was reported to occur in 7% to 30% of pediatric
patients with differentiated TC (DTC) and ∼4% of pediatric patients with DTC in the
adult group.[4] The metastatic sites of TC are mainly distributed in the lung, bone, liver,
and brain. Among these sites, the long-term overall survival of patients with
pulmonary metastases (PMs) ranges from 25% to 75%.[5] The incidence of bone metastases, the second most common site, was reported
to be in the range of 1% to 20%.[6] According to the 2018 National Comprehensive Cancer Network guidelines,
conventional treatments for DM include radioactive iodine (RAI), external beam
radiation therapy (EBRT), and chemotherapy. Excluding central nervous system being
recommended to neurosurgical resection, all soft tissue metastases were recommended
to RAI. After iodine diagnostic imaging, confirmed radioiodine-avid tumors will be
subjected to RAI. On the other hand, metastatic disease not amenable to RAI therapy
will be treated by EBRT. External beam radiation therapy was found to improve
disease-free survival at 10 years.[7] According to a meta-analysis, EBRT also decreased locoregional recurrence
from 25% to 8%.[8] However, it was still debated whether EBRT could benefit metastatic patients.
Although the indications for RAI and EBRT might explain the survival difference,
some study suggested that RAI inherently conferred better prognosis, while EBRT
conferred worse prognosis.[9] The present tumor classifications cannot identify the patients who bear
RAI-refractory tumors. Predicting the success of this therapeutic is difficult.Generally, RAI is recommended for patients with such clinical indications as tumor
size ≥20 mm, high-risk histology, extrathyroidal extension (EE), lymph node
metastases, multifocality, and unstimulated serum thyroglobulin (Tg).[10,11] As strongly recommended in the 2015 American Thyroid Association Management
Guidelines, RAI should be applied to treat patients with TC undergoing PM. The
efficacy rate of RAI therapy has been proven to be 58% in cases with PM.[12] It is reported that patients with PM after RAI are more likely to have a
better prognosis by the presence of young patients, low serum Tg level,
nonextrapulmonary DM, 131I-avid lung nodules, and pulmonary lesion size
<1 cm.[12-15] However, to date, the detailed indication of RAI in patients with TC having
DM has not been assessed for its ability to predict survival nor has it been tested
among patients undergoing other treatments.The purpose of our investigation was to evaluate survival trends and differences in a
large cohort of patients with TC with DMs treated with RAI or EBRT.
Materials and Methods
From the Surveillance, Epidemiology, and End Results (SEER) program, we identified
patients with TC diagnosed from 2010 to 2016 and excluded those who were diagnosed
with more than 1 primary tumor. We chose 2010 as the start point for the information
of DM that was available from 2010. The demographic characteristics included age at
diagnosis (≤45 years and >45 years) and sex (male and female). The patient
characteristics included grade (well-differentiated, moderately differentiated,
poorly differentiated, undifferentiated, and unknown), histology (according to the
International Classification of Diseases for Oncology, Third
Edition, codes 8050/3, 8052/3, 8130/3, 8260/3, 8341/3, 8342/3, 8343/3,
8344/3, 8347/3, 8408/3, 8450/3, 8452/3, 8460/3, and 8507/3 were defined as papillary
histology; code 8340/3 was defined as papillary with follicular variant histology;
codes 8345/3, 8346/3, 8347/3, and 8510/3 were defined as follicular histology; and
codes 8020/3 and 8805/3 were defined as undifferentiated histology), lymphatic
metastases (LMs; absent, present), tumor size (≤10, 11-20, 21-40, >40 mm), EE
(absent, present), and DMs (absent, present). Based on surgical treatments, patients
were categorized as receiving total thyroidectomy (surgery of primary site variable
values of 50), receiving other surgery (surgery of primary site variable values of
10-40), refusing surgery (surgery of primary site variable values of 00), and
unknown (surgery of primary site variable values of 80-99). Based on radiotherapy,
patients were categorized as receiving radioiodine (radiation recode variants of
radioisotopes), receiving beam radiation, refusing radiotherapy, and others.
Statistical Analysis
Clinical characteristics were compared using the χ2 test or Fisher
exact test as appropriate. Logistic regression and Cox regression analysis were
used to model the risk factors of DMs and prognostic factors of patients with DM
and PM. Odds ratios (ORs) or hazard ratios (HRs) and 95% confidence intervals
(CIs) were calculated for the corresponding model. All variants selected into
the multivariate models were calculated to be significant at the <.05 level
in advance. Analyses were performed with SPSS version 22.0 (IBM Corporation,
Armonk, New York), and all charts were performed with GraphPad Prism 8.0.
Thyroid cancer–specific survival (TCSS) only analyzed the percentage of people
who died from TC. Patients who died from causes other than TC were not counted.
A 2-side P value <.05 was considered to be statistically
significant.
Results
Clinical Characteristics and Risk Factors for Patients With DM
During the 2010 to 2016 period, a total of 75 419 patients were enrolled in the
study. Among these patients, DM was found in 1608 cases. The patients with DM
were divided into 5 main groups according to metastatic sites: 521 (32.4%) cases
with bone metastasis, 90 (5.6%) cases with brain metastasis, 158 (9.8%) cases
with liver metastasis, 995 (61.9%) cases with lung metastasis, and 50 (3.1%)
cases with other metastases. Of these patients with DM, 759 (47.2%) died of TC.
The mean follow-up at the time of death was 36.07 months, and the median
follow-up was 34.00 months.The characteristics of the patients with TC with DM are provided in Table 1. DM was more
common in patients aged >45 years (3.8%) and male (4.9%) compared to the
non-DM group. A total of 52.9% of undifferentiated patients had DM. In advance,
DTC, smaller tumor size, less lymph node involvement, and EE were less diagnosed
with DM. A total of 32.4% of patients who refused the surgery had DM, while
almost none of the patients who underwent thyroidectomy (total thyroidectomy
1.5%, others 1.3%) had DM. A total of 40.9% patients who underwent EBRT had DM,
while only 1.6% patients who underwent RAI had DM.
Table 1.
Clinical Characteristics of the Patients With TC With DM.
Clinical Characteristics of the Patients With TC With DM.Abbreviations: DM, distant metastasis; EBRT, external beam radiation
therapy; RAI, radioactive iodine; TC, thyroid cancer.Multivariate logistic regression analysis was applied to assess the various risks
stratified by DM status (Figure
1). Compared with patients aged ≤45 years, the cases aged >45
years (adjusted OR [aOR]: 2765; 95% CI: 1.959-3.903] had an increased risk of
DM. Referred to patients in well-differentiated tumors, patients in higher
grades (moderately, aOR: 1.685; 95% CI: 1.138-2.495, poorly, aOR: 6.398; 95% CI:
4.333-9.448, undifferentiated, aOR: 12.861; 95% CI: 8.175-20.235) showed an
uptrend in the possibility of DM. In addition, DM was less frequently associated
with females (aOR: 0.754; 95% CI: 0.584-0.972), significantly associated with
papillary with follicular variant histology (vs papillary, aOR: 1.711; 95% CI:
1.182-2.476), follicular histology (vs papillary, aOR: 4.849; 95% CI:
3.085-7.622), LM (vs without LM, aOR: 3.435, 95% CI: 2.588-4.559), tumor size
>20 mm (21-40 mm vs ≤10 mm, aOR: 2.068; 95% CI: 1.176-3.639; >40 mm vs ≤10
mm, aOR: 4.647; 95% CI: 2.649-8.152), and EE (vs intrathyroidal extension, aOR:
2.179; 95% CI: 1.612-2.946). Ultimately, multivariate analysis revealed that age
46 to 85, male, higher grades, papillary with follicular variant histology,
follicular histology, tumor size >20 mm, LM, and EE all significantly
increased DM hazard compared with the counterpart.
Figure 1.
Multivariable logistic regression for analyzing the risk factors for DM
in patients diagnosed with TC. *P values significant at
the <.05 level. aOR indicates adjusted odds ratio (adjusted for age,
sex, grade, histology, LM, tumor size, and EE); CI, confidence interval;
DM, distant metastasis; EE, extrathyroidal extension; IE, intrathyroidal
extension; LM, lymphatic metastases; TC, thyroid cancer; y, years.
Multivariable logistic regression for analyzing the risk factors for DM
in patients diagnosed with TC. *P values significant at
the <.05 level. aOR indicates adjusted odds ratio (adjusted for age,
sex, grade, histology, LM, tumor size, and EE); CI, confidence interval;
DM, distant metastasis; EE, extrathyroidal extension; IE, intrathyroidal
extension; LM, lymphatic metastases; TC, thyroid cancer; y, years.
Clinical Characteristics and Risk Factors for Different Metastatic
Sites
As shown in Table 2,
multiple characteristics as the variables were significantly associated with all
4 common sites of relapse. To further delineate the potential relationship
between characteristics and the sites of distant relapse, each of these organs
was analyzed separately (Figure
2).
Table 2.
Clinical Characteristics of Different Metastatic Sites in Patients With
TC.
Multivariable logistic regression for analyzing the risk factors for bone
metastases (A), brain metastases (B), liver metastases (C), and lung
metastases (D). *P values significant at the <.05
level. aOR indicates adjusted odds ratio [(A), (C) and (D) are adjusted
for age, sex, grade, histology, LM, tumor size and EE. (B) is adjusted
for sex, grade, histology, LM, tumor size and EE]; CI, confidence
interval; EE, extrathyroidal extension; IE, intrathyroidal extension;
LM, lymphatic metastases; y, years.
Clinical Characteristics of Different Metastatic Sites in Patients With
TC.Abbreviations: EBRT, external beam radiation therapy; RAI,
radioactive iodine; TC, thyroid cancer.Multivariable logistic regression for analyzing the risk factors for bone
metastases (A), brain metastases (B), liver metastases (C), and lung
metastases (D). *P values significant at the <.05
level. aOR indicates adjusted odds ratio [(A), (C) and (D) are adjusted
for age, sex, grade, histology, LM, tumor size and EE. (B) is adjusted
for sex, grade, histology, LM, tumor size and EE]; CI, confidence
interval; EE, extrathyroidal extension; IE, intrathyroidal extension;
LM, lymphatic metastases; y, years.Bone metastases were significantly associated with >45 years of age, poorly
differentiated and undifferentiated, papillary with follicular variant
histology, follicular histology, LM, tumor size >10 mm, and EE, which were
less associated with females. Brain metastases were only associated with
follicular histology. Liver metastases were significantly associated with poorly
differentiated and undifferentiated tumors, medullary histology, and LM. Lung
metastases were significantly associated with >45 years of age, higher
grades, follicular histology, LM, tumor size >10 mm, and EE.It is worth noting that there was statistical significance among different
histology types for all 4 metastatic sites, and 3 of them, including bone,
brain, and lung, were associated with follicular histology. Tumor grade was
divided into 2 groups: one group consisted of well-differentiated and moderately
differentiated tumors. The other group consisted of poorly differentiated and
undifferentiated tumors. The latter was significantly associated with DM and
excluded brain metastases. Finally, the presence of LM, tumor size >10 mm,
and EE was common risk factors for bone and lung metastases.
Radioactive Iodine Improves TCSS in the Age ≤45 Years Subgroup in Patients
With DM
It is worth noting that age and grade were highlighted as common risk factors in
usual metastatic sites. Whether radiotherapy can relieve the tumor burden in
these high-risk groups is demonstrated below. Figure 3 illustrates the multivariate Cox
regression analysis of TCSS in patients with DM and PM based on age. In patients
with DM (Figure 3A and
B), among those ≤45 years of age, patients who underwent RAI had a 5-year
rate of TCSS of 91.7%, whereas those who underwent EBRT had a rate of 45.5%,
which was significantly lower than RAI (EBRT vs RAI, adjusted hazard ratio
[aHR]: 5.499, 95% CI: 1.672-18.804, P = .005). Among patients
older than 45 years, those who underwent RAI had a 5-year rate of TCSS of 69.1%
compared with 20.0% among those who underwent EBRT. However, no statistically
significance was shown in this subgroup (EBRT vs RAI, aHR: 1.801, 95% CI:
0.855-3.796, P = .122). For lung metastases (Figure 3C and D), in the
age <45 years subgroup, those who underwent RAI had significantly higher TCSS
(5 years, 94.7%) than those who underwent EBRT (5 years, 44.4%; EBRT vs RAI,
aHR: 5.386, 95% CI: 1.092-26.552, P = .039). In the age >45
years subgroup, those who underwent RAI had a 5-year rate of TCSS of 59.8%, when
EBRT had a rate of 11.8%; however, it was not significantly different (EBRT vs
RAI, aHR: 1.399, 95% CI: 0.555-3.522, P = .477). In general,
the effect of RAI in patients with PM corresponded with that in patients with
DM. Radioactive iodine was superior to EBRT in those who were younger than 45
years. In advance, we further analyzed the survival in bone metastases
(Supplementary Figure 1), but no significance was observed.
Figure 3.
Multivariate Cox regression analysis survival curves of TCSS based on age
subgroup. A, Age ≤45 years in patients with DM. Adjusted for histology
and surgical treatments. B, Age >45 years in patients with DM.
Adjusted for grade, histology, surgical treatments, LM, tumor size, and
EE. C, Age ≤45 years in patients with PM. Adjusted for histology and
surgical treatments. D, Age>45 years in patients with PM. Adjusted
for grade, histology, and surgical treatments. DM indicates distant
metastasis; EE, extrathyroidal extension; LM, lymphatic metastasis; PM,
pulmonary metastasis; TCSS, thyroid cancer–specific survival.
Multivariate Cox regression analysis survival curves of TCSS based on age
subgroup. A, Age ≤45 years in patients with DM. Adjusted for histology
and surgical treatments. B, Age >45 years in patients with DM.
Adjusted for grade, histology, surgical treatments, LM, tumor size, and
EE. C, Age ≤45 years in patients with PM. Adjusted for histology and
surgical treatments. D, Age>45 years in patients with PM. Adjusted
for grade, histology, and surgical treatments. DM indicates distant
metastasis; EE, extrathyroidal extension; LM, lymphatic metastasis; PM,
pulmonary metastasis; TCSS, thyroid cancer–specific survival.
Radioactive Iodine Improves TCSS in the Well-Differentiated and Moderately
Differentiated Grade Subgroup in Patients With DM
Among patients with DM in well- and moderately differentiated tumor grade, those
who received RAI had a 5-year rate of TCSS of 78.9%, compared with a rate of
64.8% among those who underwent EBRT (EBRT vs RAI, aHR: 2.975, 95% CI:
1.044-8.476, P = .041; Figure 4A). However, among patients with
poor or undifferenced grade, there was no significant difference between the RAI
(5 years, 38.9%) and EBRT (5 years, 6.4%) groups with respect to TCSS (Figure 4B; EBRT vs RAI,
aHR: 1.678, 95% CI: 0.757-3.721, P = .203). Conversely, among
patients with PM (Figure 4C and
D), no statistically significant difference was observed in the
better differentiated group (EBRT vs RAI, aHR: 2.472, 95% CI: 0.504-12.131,
P = .265) when RAI increased TCSS compared with EBRT in the
higher grade group (EBRT vs RAI, aHR: 3.413, 95% CI: 1.707-6.821,
P = .001). This finding does not demonstrate any advantage
of RAI therapy on the basis of grade classification among patients with DM at
high grade since these patients have no benefit from the use of adjuvant RAI,
but RAI improves the TCSS of patients with PM in poor grade tumors. Furthermore,
we analyzed the survival in bone metastases (Supplementary Figure 2), but no
significance was observed in the survival rate between different groups.
Figure 4.
Multivariate Cox regression analysis survival curves of TCSS based on
grade subgroup. A, Well- and moderately differentiated tumors in
patients with DM. Adjusted for age and surgical treatments. B, Poorly
differentiated and undifferentiated tumors in patients with DM. Adjusted
for age, histology, surgical treatments, LM, and EE. C, Well- and
moderately differentiated tumors in patients with PM. Adjusted for
surgical treatments. D, Poorly differentiated and undifferentiated
tumors in patients with PM. Adjusted for age, histology, and surgical
treatments. DM indicates distant metastasis; EE, extrathyroidal
extension; LM, lymphatic metastasis; PM, pulmonary metastasis; TCSS,
thyroid cancer–specific survival.
Multivariate Cox regression analysis survival curves of TCSS based on
grade subgroup. A, Well- and moderately differentiated tumors in
patients with DM. Adjusted for age and surgical treatments. B, Poorly
differentiated and undifferentiated tumors in patients with DM. Adjusted
for age, histology, surgical treatments, LM, and EE. C, Well- and
moderately differentiated tumors in patients with PM. Adjusted for
surgical treatments. D, Poorly differentiated and undifferentiated
tumors in patients with PM. Adjusted for age, histology, and surgical
treatments. DM indicates distant metastasis; EE, extrathyroidal
extension; LM, lymphatic metastasis; PM, pulmonary metastasis; TCSS,
thyroid cancer–specific survival.
Discussion
Using a large population of patients with advanced TC, this study illustrated that
age >45, higher grades, papillary with follicular variant histology, follicular
histology, LM, tumor size >20 mm, and EE were risk factors for DM independent of
other clinicopathological factors. Furthermore, these observations illuminate the
significant impact of age >45 years and higher grades on metastatic spread and
thus reinforce further their clinically relevant implications. Our findings on the
association between RAI and survival indicated that RAI could significantly improve
survival in age ≤45 years and well-/moderately differentiated grade subgroups in
patients with DM, as well as in patients with PM who are younger than 45 years or
with poor grade tumors.Risk factors for DM have been discussed in some studies. A previous study indicated
that patients >65 years of age and follicular and medullary TC were risk factors
for bone metastases.[16] Patients with papillary TC who were older, male, with larger tumor size and
higher Tg level had a higher risk of PM.[17] For other metastatic sites, little information was published. As the
supplement, our study provided evidence that worse grade, tumor size >10 mm, LM,
and EE were also associated with bone metastasis development. Poor grade, follicular
histology, LM, and EE were correlated with lung metastases. In addition, risk
factors for liver and brain metastases are listed. Apart from these clinical
characteristics, gene mutations also take part in DM. Undifferentiated tumors had a
greater mutation burden, including TP53, TERT promoter, PI3K/AKT/mTOR pathway,
SWI/SNF subunits, and histone methyltransferases. BRAF and RAS were predominantly
mutated genes, which dictated distinct metastatic sites. The BRAF mutation led to
regional nodal metastases, and the RAS mutation tended to DMs.[18]Age >45 years was a negative prognostic factor for the survival of patients with
DM and PM undergoing RAI. Because EBRT was regularly recommended to
radioiodine-refractory patients, we compared the survival of these 2 radiotherapy
treatments to explore the clinical characteristics of RAI-refractory population.
Existing studies have suggested that RAI could improve the survival of patients with
TC with PM.[5,19,20] The younger patients showed stronger RAI avidity[1,21] for the more active expression of the sodium iodide symporter.[12] In addition, the decline of the immune system and the more aggressive
histological subtype also accounted for the poor effect of RAI in the older patients.[15,22] Moreover, the possible hypofunction of the hypothalamic/pituitary system
resulted in a decreased response to the low level of serum T4, which gave rise to
insufficient serum thyroid-stimulating hormone (TSH),[23] subsequently impairing RAI uptake. Relevant evidence about the correlation
between the effect of RAI and serum thyrotropin (TSH) level in young group and aged
group was insufficient, so this hypofunction should be further discussed.Regarding the other risk and negative prognostic factors of patients with DM, poor
tumor grade results in RAI-refractory tumors in most cases. Based on our study, RAI
significantly improved the survival of patients with DM in the better grade subgroup
but failed in the higher grade subgroup. In theory, poorly differentiated or
undifferentiated thyroid tumors rarely concentrate iodine,[24] which represents the low efficacy of RAI. The conventional therapy of
radiosensitizing combined with adjuvant chemotherapy seemed to be ineffective in
metastatic anaplastic TC.[25,26] Thus, we compromised EBRT in progressive or symptomatic disease. However, we
obtained contradictory results in patients with PM. The BRAFV600E mutation might
explain this phenomenon. BRAFV600E knockdown in mice resulted in fewer lung
metastases from primary tumors,[27] which proved that BRAF activation was associated with lung metastases. The
BRAFV600E mutation could activate the MAP kinase pathway, which resulted in a
decreased expression of sodium iodide symporter.[28] A new study suggested that MAPK pathway inhibition or BRAF inhibitor could
inverse RAI-refractory TC.[29] On the other hand, the effect of RAI in poorly differentiated patients with
PM might be explained by the well-differentiated variant of metastatic lesions,
which need further study and more evidence. Furthermore, the dose of radioiodine
could make difference. Generally, lymph node metastases may be treated with about
100 to 175 mCi of 131I. Patients with DMs are usually treated with 100 to
200 mCi of 131I, when diffuse PMs are recommended less to avoid lung
injury. We further analyzed survival difference in patients with PM based on lymph
node status (Supplementary Figure 3), but no statistical significance was observed.
According to our results, careful selection was required for patients with PM with
lower grades.The study has several limitations. Distant metastases and nondifferentiated thyroid
carcinoma in TC are sufficiently rare that the sample size of this study was small.
Due to the insufficient number of cases of some subgroups, bias was unavoidable, and
further study was not performed. Also, some follow-up data, such as the level of
serum Tg and recurrence, are not available in the SEER program.
Conclusions
In conclusion, age and grade not only suggest a high risk of DM but are also
significantly different regarding the effect of radiotherapy on tumors. These
observations could potentially be used in determining the appropriate regimen for
patients with TC with DM.Click here for additional data file.Supplemental Material, s1 for Radioactive Iodine Therapy in Patients With Thyroid
Carcinoma With Distant Metastases: A SEER-Based Study by Chenyuan Li, Qi Wu and
Shengrong Sun in Cancer ControlClick here for additional data file.Supplemental Material, s2 for Radioactive Iodine Therapy in Patients With Thyroid
Carcinoma With Distant Metastases: A SEER-Based Study by Chenyuan Li, Qi Wu and
Shengrong Sun in Cancer ControlClick here for additional data file.Supplemental Material, s3 for Radioactive Iodine Therapy in Patients With Thyroid
Carcinoma With Distant Metastases: A SEER-Based Study by Chenyuan Li, Qi Wu and
Shengrong Sun in Cancer Control
Authors: Jessica D Kondraciuk; Samuel L Rice; Xiaosun Zhou; Karem Gharzeddine; Andrea Knezevic; Daniel E Spratt; Mona Sabra; Steven M Larson; Ravinder K Grewal; Joseph R Osborne Journal: Clin Nucl Med Date: 2019-08 Impact factor: 7.794
Authors: Carmelo Nucera; Alessandro Porrello; Zeus Andrea Antonello; Michal Mekel; Matthew A Nehs; Thomas J Giordano; Damien Gerald; Laura E Benjamin; Carmen Priolo; Efisio Puxeddu; Stephen Finn; Barbara Jarzab; Richard A Hodin; Alfredo Pontecorvi; Vânia Nose; Jack Lawler; Sareh Parangi Journal: Proc Natl Acad Sci U S A Date: 2010-05-24 Impact factor: 11.205
Authors: Robert C Smallridge; Kenneth B Ain; Sylvia L Asa; Keith C Bible; James D Brierley; Kenneth D Burman; Electron Kebebew; Nancy Y Lee; Yuri E Nikiforov; M Sara Rosenthal; Manisha H Shah; Ashok R Shaha; R Michael Tuttle Journal: Thyroid Date: 2012-11 Impact factor: 6.568
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