الفهرس 
Thyroid glandOnly 14 pages are availabe for public view
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Abstract
Currently, thyroid carcinoma is a common endocrine neoplasm, and the population of newly diagnosed, low-stage cancers is constantly growing. Therefore, current recommendations on the therapeutic strategy (especially in this stage) should be updated and modified to avoid overdiagnosis and overtreatment and to prevent the worsening of treatment results. Of note, reduction in adverse effects is also a key aspect of therapy to improve patients’ quality of life.
Thyroid cancer can be classified into four main histological types: papillary, follicular, medullary, and anaplastic. Among these, papillary thyroid carcinoma (PTC) is the most prevalent, accounting for around 80-85% of all thyroid cancers.
The lack of prospective randomized clinical trials results in the fact that the majority of the current recommendations are based on retrospective studies, meta-analyses, or expert opinions. Therefore, for many years, the optimal extent of surgical treatment in differentiated thyroid carcinomas has been a subject of debate.
Surgical management is the primary treatment for thyroid cancer, and total thyroidectomy is considered the gold standard for the management of papillary thyroid carcinoma. The goal of surgery is to remove all cancerous tissue while preserving the parathyroid glands and the recurrent laryngeal nerves.
The majority of patients with thyroid cancer are at low risk for recurrence (<5%),1-3 and their risk of cancer-related death is even lower. After thyroidectomy, radioiodine (iodine-131) is generally administered both to ablate residual normal thyroid tissue and to treat persistent disease.
There is a consensus to avoid radioiodine administration in patients with a unifocal microcarcinoma (≤10 mm in diameter), but the benefits of radioiodine administration in other patients with low-risk thyroid cancer remain controversial.
Given that the effectiveness and safety of thyroidectomy without radioiodine therapy in patients with low-risk Papillary thyroid carcinoma was still unclear, further study is needed. Meta-analysis is a method of summarizing similar research results, which can expand the sample size and improve statistical validity, especially in the case of inconsistent results from previous studies. Meta-analysis has the ability to obtain results based on existing research results, and comprehensive analysis, which would be closer to real life.
The main aim of this systematic review and meta-analysis was to evaluate the efficacy of thyroidectomy without radioiodine therapy in patients with low-risk papillary thyroid carcinoma.
This systematic review and meta-analysis included 10 studies with a total of 23581 patients with low grade papillary thyroid cancer (PTC). A total of 14384 patients underwent thyroidectomy followed by radioactive iodine (RAI) ablation, whereas 9197 patients underwent thyroidectomy without RAI ablation.
The main results of the study revealed that:
• All patients in the study by Eto et al did not receive RAI postoperatively. In the remaining studies, the proportion of patients who received RAI ablation ranged from 29% to 86%, whereas 14% 71% patients did not. Participants’ mean age was reported in all studies ranging from 41 to 52.2 years in the RAI group, and from 41 to 52.6 years in the No-RAI group. In the study by Creach et al., (2012)79% patients were females. In the remaining studies, the overall female percentage ranged from 6% to 90% in the RAI group, and from 73% to 94% in the No-RAI group.
• All patients had pure thyroid papillary carcinoma or microcarcinoma, except for Creach et al. who reported 87 patients with follicular variant, and four patients with tall cell variant, Jeon et al. who reported 28 patients with follicular variant, and Leboulleux et al. who reported 24 patients with follicular variant, and eight patients with oncocytic variant.
• Regarding risk stratification tool, six studies used the American Thyroid Association (ATA) staging, four studies used the TNM staging, two studies used the Memorial Sloan Kettering Cancer Centre (Grade, Age, Metastases, Extent, Size or GAMES) system, and one study used the Metastases, Age, Completeness of Resection, Invasion, Size (MACIS) system.
• All patients underwent total or near total thyroidectomy except for 1601 (61%) in the study by Ito et al, and 27 (6.6%) patients in the study by Creach et al. who underwent partial thyroidectomy. Elective cervical lymph node dissection was reported by five studies.
• The mean tumour sized was reported in six studies, ranging from 0.6 to 2.1 cm in the RAI group, and from 0.6 to 1.9 cm in the No-RAI group. In the study by Eto et al, 37% tumours were multicentric, 21% had extrathyroid extension, and 42% showed lymphatic invasion. In the study by Creach et al, 46% tumours were multicentric, 31% had extrathyroid extension, and 7% showed lymphatic invasion. In the remaining studies, Multicentricity was reported in 31-50% in the RAI group, and 12-40% in the No-RAI group. Extrathyroid extension was reported in 5-70% in the RAI group, and 1-72% in the No-RAI group. LN invasion was reported in 2-91% in the RAI group, and 1-88% in the No-RAI group.
• All observational retrospective studies were evaluated by the Methodological Index for Non-Randomized Studies (MINORS) which consists of eight criteria for non-comparative studies and 12 criteria for comparative studies. Each study scored 0-2 points for each of these items. all included studies showed moderate to high methodological quality. The risk of bias assessment for RCT by Leboulleux et al. had been carried out using the Cochrane Collaboration’s quality assessment tool. The study showed low risk for selection bias, attrition bias, and reporting bias, and high risk for performance bias and detection bias due to lack of blinding of participants and personnel and outcome measurements.
• Nine studies reported on the overall survival rate for patients not receiving RAI ablation. A random effect model was used as significant heterogeneity was detected (I² = 97%, P < 0.001). The overall survival rate ranged from 0.79 to 1.00, with the pooled estimate being 0.94 (95% CI: 0.90 – 0.96).
• Eight studies compared the overall survival rates between the two groups, with 13874 patients in the RAI group and 5475 patients in the No-RAI group. A signficant hetergeneity was detected. Therefore, a random-effect model was used for analysis (I² = 94%, P < 0.001). The combined OR and 95% CIs was 0.99 (0.44 to 2.23). The combined result demonstartes no statistically significant difference between groups in terms of short-term or long-term survival rates (Z = 0.03, P = 0.97).
• Ten studies reported on the recurrence rate for patients not receiving RAI ablation. A random effect model was used as significant heterogeneity was detected (I² = 94%, P < 0.001). The recurrence rate ranged from 0 to 0.34, with the pooled estimate being 0.05 (95% CI: 0.02 – 0.09).
• Eight studies compared the recurrecne rates between the two groups, with 2177 patients in the RAI group and 2224 patients in the No-RAI group. A signficant hetergeneity was detected. Therefore, a random-effect model was used for analysis (I² = 90%, P < 0.001). The combined OR and 95% CIs was 0.98 (0.43 to 2.83). The combined result demonstartes no statistically significant difference between groups in terms of recurrence rates (Z = 0.03, P = 0.98).
• Six studies identified predictors of recurrence, including positive nodal status (four studies), large size (three studies), limited thyroidectomy (Ito et al), RAI (Creach et al), high thyroglobulin (Leboulleux et al), multicentricity, and extrathyroid extension (Zhao et al). Table 7 summarzies the diagnostic tools for detection of recurrence and its distribution in the included studies.
• Four studies reported on the reintervention rate for patients not receiving RAI ablation. A random effect model was used as significant heterogeneity was detected (I² = 94%, P < 0.001). The reintervnetion rate ranged from 0 to 0.09, with the pooled estimate being 0.01 (95% CI: 0.00 – 0.08).
• Three studies compared the recurrecne rates between the two groups, with 605 patients in the RAI group and 631 patients in the No-RAI group. No signficant hetergeneity was detected. Therefore, a fixed-effect model was used for analysis (I² = 0%, P = 0.37). The combined OR and 95% CIs was 1.58 (0.84 to 2.98). The combined result demonstartes no statistically significant difference between groups in terms of reintervention rates (Z = 1.42, P = 0.15).
• Seven studies reported on the mortality rate for patients not receiving RAI ablation. A random effect model was used as significant heterogeneity was detected (I² = 70%, P = 0.003). The mortality rate ranged from 0 to 0.01, with the pooled estimate being 0.00 (95% CI: 0.00 – 0.01).
• Six studies compared the mortality rates between the two groups, with 13377 patients in the RAI group and 5221 patients in the No-RAI group. A signficant hetergeneity was detected. Therefore, a random-effect model was used for analysis (I² = 84%, P = 0.01). The combined OR and 95% CIs was 4.14 (0.12 to 147.21). The combined result demonstartes no statistically significant difference between groups in terms of mortality rates (Z = 0.78, P = 0.44).
Conclusion
In conclusion; the current systemic review and meta-analysis showed that the radioactive iodine (RAI) ablation post thyroidectomy among Low-risk PTC patients on reintervention rate have no significant impact on survival, recurrence, reintervention or mortality rates.
According to the existing data positive nodal status, large size, limited thyroidectomy, RAI, high thyroglobulin, multicentricity, and extrathyroid extension were identified as significant predictors of recurrence.
A controlled multicenter prospective trial looking at the effect of RAI on recurrence and mortality is needed to mitigate the factors limiting our current results.
Recommendations
It is recommended that future studies be conducted using well-designed randomized controlled trials or large, comparative observational studies.
Inclusion a representative sample of patients with similar age, gender, and disease severity.
Data collection using standardized tools and protocols, at regular intervals postoperatively.
The sample size of future studies should be large enough to provide meaningful conclusions and to control for confounding factors.
To accurately assess long-term outcomes, studies should have a longer follow-up period.
We recommended that future research should include multicenter studies to validate our findings