Keywords Radioiodine ablation - surgical volume - thyroid cancer - thyroidectomy
Introduction
Thyroid cancer is one of the most common endocrine malignancies, with an increasing
incidence during the last decades. Differentiated thyroid cancer (DTC) comprising
>95% of all of the thyroid cancer and is generally associated with an excellent prognosis.[1 ],[2 ],[3 ]
Ablation with radioiodine (I-131) following thyroidectomy is the widely accepted therapeutic
procedure for DTC with the aims of removal remained thyroid tissues after thyroidectomy,
prolong disease-free survival, and also treating high-risk patients with persistent
tumor.[4 ]
According to the literature, surgical volume and precise dose of radioiodine have
a great impact on the results of the treatment procedure. Several studies revealed
better treatment outcomes for high-volume surgeons for thyroid surgery. It has been
shown that thyroid surgery with the high-volume surgeon has less surgical complications,
lower readmission rate, and also shorter hospitalization.[5 ],[6 ],[7 ]
Besides its advantages in the removal of residual thyroid tissue, radioiodine presents
potential risks on normal tissues.[4 ] According to the 2015 American Thyroid Association (ATA), the DTC patients for the
evaluation of the risk of postsurgery recurrence were classified into low-, intermediate-,
and high-risk groups.[8 ] Nowadays, radioiodine therapy (RIT) after thyroidectomy is well accepted for high-risk
DTC patients. It is controversial for low- and intermediate-risk patients. RIT in
low and intermediate patients is performed mainly for residual thyroid tissue ablation.
Previously, a fixed dose of radioiodine “commonly 3.7 GBq (100 mCi)” was used in these
DTC patients. However, recent publications have reported almost similar results of
ablation with 1.1 GBq (low dose) compared to 3.7 GBq (high dose) of radioiodine in
low- and intermediate-risk patients after total thyroidectomy (TT) or near total thyroidectomy
(NTT).[4 ],[9 ],[10 ]
The aim of this study was to evaluate the impact of surgical volume and radioiodine
doses (low vs. high doses) on the treatment outcome of low-risk DTC patients.
Materials and Methods
Patients
This quasi-experiment study included 78 DTC patients aged from 18 to 78 years old
who were referred from the Research Institute for Endocrine Sciences to the Department
of Nuclear Medicine in a tertiary university-affiliated hospital from October 2016
to January 2019. Inclusion criteria included age ≥18 and low-risk DTC (tumor stage
T1–T3 with or without lymph node involvement but no distant metastasis). Exclusion
criteria included patients with distant metastasis, patient without surgery of TT,
cases with intermediate to high-risk stratification according to the ATA 2015, patients
with a history of RIT, and patients with insufficient data. An informed consent form
was signed by each patient for entering the study. The study was approved by the ethics
committee of Shahid Beheshti University of Medical Sciences (Registration No: IR.SBMU.MSP.REC.1397.132).
Study procedures
The patients were classified into four groups: (1) Thyroid ectomy was performed by
thyroid surgeon and low-dose (1850 MBq [30 mCi]) radioiodine was administered (n = 17), (2) Thyroidectomy was performed by thyroid surgeon and high-dose (3700 MBq
[100 mCi]) radioiodine was administered (n = 10), (3) Thyroidectomy was performed by general surgeon, and low-dose radioiodine
was administered (n = 22) and (4) Thyroidectomy was performed by a general surgeon and high-dose radioiodine
was administered (n = 29) [Figure 1 ].
Figure 1 Flow-chart of research design
All patients underwent TT. Lymph node dissection was performed for patients showing
lymph-node involvement. The patients were asked to discontinue levothyroxine and have
a low iodine diet for 1 month before ablation. For each patient, preablation tests
were performed, including clinical history, physical examination, thyroid-stimulating
hormone (TSH), serum thyroglobulin (Tg), serum anti-Tg, neck ultrasonography, and
chest X-ray.
We defined the thyroid surgeon when a surgeon performs at least 100 thyroid operations
annually. Those who perform <100 thyroid surgery we define them as general surgeons.
After the administration of radioiodine, all patients were hospitalized in isolation
rooms until the dose rate decreased to 30 mSv/h at a distance of one meter measured
by a Geiger counter and clinical conditions allowed discharge. I-131 whole-body scan
(WBS) was performed 5–7 days after ablation with a dual-head gamma camera (Philips
(ADAC) Vertex Plus) equipped with high energy parallel-hole collimators.
Follow up
The patients were followed for at least 6 months after ablation. Follow up neck ultrasonography,
TSH-off levothyroxine, Tg-off levothyroxine and anti-Tg-off levothyroxine tests were
performed for evaluation of ablation success. The ablation was considered complete
response when: (i) serum Tg-off ≤2 ng/mL, (ii) no abnormal activity throughout the
body on follow-up diagnostic imaging including neck ultrasonography and I-131 WBS.
In addition, two common side effects associated with radioiodine ablation, including
dry mouth, nausea, vomiting, were evaluated in all patients.
Statistical analysis
The sampling method was based on nonprobability sampling. The study was done as a
control group pretest-posttest design. All quantitative data were presented as the
mean ± standard deviation., with ranges given when proper. The qualitative data were
expressed as a percentage. A Chi-square test was used for the analysis of qualitative
variables, and t-test was applied for quantitative values. The Mann–Whitney U-test
also was used when the data did not approximate a normal distribution. SPSS v 20 (SPSS,
Inc., IBM Corporation, Somers, NY, USA) was used for statistical analysis. P <0.05
was considered statistically significant difference.
Results
Patients
In total, 78 low-risk DTC patients (female: 70 [89.7%]; male: 8 [10.3%]) aged from
18 to 78 years old with a mean of 41.96 ± 13.42 years old were enrolled in this study.
The clinical characteristics of patients are shown in [Table 1 ].
Table 1 Patients baseline characteristics
In the initial assessment, the mean values of TSH, Tg, and anti-Tg were 76.64 ± 55.54
μIU/L, 3.68 ± 6.80 ng/mL and 101.58 ± 215.89 IU/mL, respectively, in all included
patients. When we divide patients into two subgroups based administered doses, there
was a significant difference in terms of tumor size (7.95 ± 4.75 vs. 17.38 ± 11.74
mm), T stage and local lymph node involvement (14 [35.9%] vs. 5 [12.8%]) (P < 0.05) [Table 1 ]. When we divide included patients into four subgroups based upon administered doses
and the surgeon's expertise, there was no significant difference among them in terms
of sex, age, initial TSH, Tg, anti-Tg, and histopathology of the tumor (P > 0.05).
When we divide patients into two subgroups based on the surgeon's experience, there
was a significant difference of preablation serum Tg level between thyroid and general
surgeons (2 (0) ng/mL vs. 4 (1) ng/mL respectively, P < 0.05). In addition, number
of dissected cervical lymph nodes was significantly higher in patients whom operated
by thyroid surgeons relative to general surgeons (11 (3) vs. 3 (0), respectively,
P < 0.05). However, the number of resected cervical lymph nodes and preablation serum
Tg levels were not associated with the final outcome (P > 0.05).
Patients with chronic thyroiditis observed on the cytopathology had the lower Tg serum
level but higher anti-Tg serum level relative to patients without that issue (Tg,
2 (0) ng/mL vs. 5 (1) ng/mL, value <0.05 and anti-Tg, 179 (48) IU/mL vs. 31 (5) IU/mL,
P value 0 <0.05, respectively). [Figure 2 ] and [Figure 3 ] show post-ablation whole-body I-131 scan in DTC patients in whom thyroidectomy was
carried out by the general surgeon and thyroid surgeon, respectively.
Figure 2 Postablation whole body I-131 scan in differentiated thyroid cancer patients (2 cases)
in whom thyroidectomy was carried out by general surgeon
Figure 3 Postablation whole body I-131 scan in differentiated thyroid cancer patients (2 cases)
in whom thyroidectomy was carried out by thyroid surgeon
Follow-up
The patients were followed for 6–12 months after ablation (mean: 9.10 ± 2.62 months).
The treatment was successful in 75/78 (96.2%) of patients. The rate of treatment success
in groups is shown in [Figure 1 ]. There was no significant difference in treatment success among groups (P > 0.05). Neither surgical volume nor administered activity had a significant influence
on treatment results (P > 0.05).
In the multivariable analysis, none of the sex, age, administered activity, type of
surgeon, histopathology of the tumor, metastasis, TT and NTT, baseline serum Tg, anti-Tg
and TSH, initial neck ultrasonography parameters, had no sole factor which independently
had a significant impact of ablation result.
Side effects
Dry mouth and vomiting/nausea were reported in 12 (15.4%) and 9 (11.5%) of all patients.
There was a significant association between administered activity and side effects.
In low dose patients, only one patient complained from dry mouth; however, 11/39 patients
who received the high dose of radioiodine complained from dry mouth (P = 0.002). In addition, 9/39 high dose patients suffered from vomiting/nausea; however,
none of the low dose patients suffered from vomiting/nausea (P = 0.001).
Discussion
In this study, we evaluated the effect of radioiodine dose and also surgical volume,
including thyroid surgeon as high volume and general surgeon as low volume on treatment
outcome in low-risk DTC patients. There was no statistical difference between treatment
outcome and the surgical volume because a large percentage of studied patients (96.2%)
showed a complete response. The success rate of the patients in this paper was very
good (96.2%). It is hard to find differences in the subjects showing homogenously
good results. It has shown that the significant impact of surgical volume on treatment
outcome of thyroid cancer was revealed in several studies.[5 ],[6 ] In a study, Al-Qurayshi et al . evaluated the association of surgical volume with clinical outcomes and costs of
thyroidectomy. They observed that the higher volume of the surgeon is related to favorable
clinical and financial outcomes.[11 ] Furthermore, Meltzer et al . assessed the impact of surgical volume on clinical outcome and surgical efficacy
in thyroid surgery. They reported that high volume surgeons provide patients with
favorable clinical outcomes and contribute to organizational efficiency.[6 ]
In this study, there was no statistically significant association between RIT outcomes
in low-risk DTC patients after surgery with low dose and high dose of radioiodine.
In correlation with our study, there were several studies that revealed no significant
difference in treatment outcomes of ablation with low and high doses of radioiodine.[4 ],[10 ],[12 ] However, in contrast to our results, Fallahi et al . performed a double-blinded randomized controlled trials and reported better treatment
outcomes in high dose (3.7 GBq) in comparison with low dose (1.1 GBq).[9 ]
In addition to treatment outcome, we evaluated the common RIT-related adverse effects,
including dry mouth and vomiting/nausea following radioiodine ablation. We observed
a significant relationship between high administered dose and adverse effects, which
was in correlation with a study performed by Qu et al .[4 ]
On the other hand, one point that precludes a strong conclusion in the current study
is that a significant difference in tumor size, T stage, and lymph node involvement
between low and high-risk patients. There are some reports that showed the T stage
has a significant impact on treatment response, which higher T stage is related to
the lower possibility of complete response in low dose DTC patients.[13 ] Therefore, our study may indicate low dose radioiodine ablation is preferred in
low-risk DTC patients with T stage <2 and without any lymph node involvement with
consideration of lower side effects, lower cost and also no need to hospitalization
in compared to high dose.
Our study has several drawbacks. The major limitation was low sample size and short
follow-up period of the study that could have a large impact on our final appraisal.
Another limitation was the impossibility of randomization, particularly on the surgeon
selection. However, further well-designed studies, especially considering the large
number of patients and long follow up to ascertain the progression-free survival and
overall survival are needed.
Conclusion
The study may show that the volume of the surgeon and administered radioiodine dose
had no significant impact on treatment outcomes in patients with low-risk DTC. In
addition, it may demonstrate that low dose radioiodine ablation is preferred for low-risk
DTC patients, especially in patients with T stage <2 without any lymph node involvement.
