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Background: Multiple targeted therapeutics are available for radioiodine-refractory differentiated thyroid cancer (RAIR-DTC), but it remains unclear which treatment is optimal to achieve long-term survival. Methods: A systematic search of the PubMed, Embase, and ClinicalTrials.gov databases was conducted to identify eligible randomized controlled trials (RCTs) comparing the efficacy and safety of targeted treatments for patients with RAIR-DTC from inception to April, 2022. Data were extracted by following the recommendations of the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. We calculated the odds ratio (OR) or hazard ratio (HR), its corresponding 95% credible intervals (CrI), and the surface under the cumulative ranking curve (SUCRA) to indicate ranking probability using Bayesian network meta-analyses. The primary outcome was progression-free survival (PFS). The secondary outcomes were overall survival (OS), objective response rate (ORR), disease control rate (DCR), and grade 3 or higher adverse events. Results: A total of 12 eligible RCTs involved 1,959 patients and 13 treatments: apatinib, cabozantinib, anlotinib, nintedanib, lenvatinib, lenvatinib with low dose (LD), sorafenib, sorafenib plus everolimus, donafenib (200 mg), donafenib (300 mg), pazopanib (continuous), pazopanib (intermittent), and vandetanib. Pooled analyses indicated that targeted therapeutics significantly prolonged PFS and OS in patients with RAIR-DTC (0.31, 0.21-0.41; 0.69, 0.53-0.85, respectively) compared with placebo. Network meta-analyses indicated that lenvatinib showed the most favorable PFS, with significant differences versus sorafenib (0.33, 0.23-0.48), vandetanib (0.31, 0.20-0.49), nintedanib (0.30, 0.15-0.60), and placebo (0.19, 0.15-0.25), while apatinib was most likely to be ranked first for prolonging OS with a SUCRA of 0.90. Lenvatinib showed the highest ORR (66%, 61%-70%), followed by anlotinib (59%, 48%-70%) and apatinib (54%, 40%-69%). Lenvatinib caused the most adverse events of grade 3 or higher, followed by lenvatinib (LD) and apatinib. Different toxicity profiles of individual treatment were also revealed. Conclusion: This network meta-analysis suggests that lenvatinib and apatinib were associated with the best progression-free survival and overall survival benefits, respectively, for patients with RAIR-DTC, compared with other targeted therapeutics. Patients who received lenvatinib or apatinib also had more grade 3 or higher adverse events. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=302249], identifier [CRD42022302249].
RESUMEN
BACKGROUND: This study aimed to clarify whether the extent of thyroidectomy (total thyroidectomy vs thyroid lobectomy) influences survival in adults with localized medullary thyroid cancer. METHODS: Patients with localized medullary thyroid cancer were identified using the Surveillance, Epidemiology, and End Results database (2000-2018). An independent cohort of patients with localized medullary thyroid cancer were retrospectively reviewed from three medical centers in China from 2010 to 2020. The patients were grouped by the extent of surgery (total thyroidectomy vs thyroid lobectomy). Primary end points were overall survival and disease-specific survival. RESULTS: From 1,686 patients with medullary thyroid cancer identified in SEER, 1,122 patients met inclusion for matching, with a median follow-up of 99 months. After propensity score matching, 122 patients underwent a total thyroidectomy and 122 patients underwent a thyroid lobectomy. The 10-year overall survival was 85.2% (77.9%-90.7%) and 83.1% (75.5%-90.7%) in total thyroidectomy group and in thyroid lobectomy group, respectively. The 10-year disease-specific survival was 100% and 96.8% (93.1%-100%) in total thyroidectomy group and in thyroid lobectomy group, respectively. There was no statistically significant difference in overall survival or disease-specific survival in patients with localized medullary thyroid cancer undergoing total thyroidectomy or thyroid lobectomy (hazard ratio = 0.83, 95% confidence interval 0.44-1.57, P = .57 and hazard ratio = 0.49, 95% confidence interval 0.10-2.41, P = .39, respectively). Forty-seven patients with localized medullary thyroid cancer were identified in an independent Chinese cohort (n = 29 in total thyroidectomy group vs n = 18 in thyroid lobectomy group). After a median follow-up of 47 months, there was no mortality observed in either group. CONCLUSION: This study suggests that the extent of thyroidectomy does not influence survival for patients with early-stage localized medullary thyroid cancer and that thyroid lobectomy might be adequate in this patient population.