Peer Review #2 of "Effect of adjuvant radioactive iodine therapy on survival in rare oxyphilic subtype of thyroid cancer (Hürthle cell carcinoma) (v0.1)"

Abstract

Radioactive iodine (RAI) is widely used for adjuvant therapy after thyroidectomy, while its value for thyroid cancer has been controversial recently. The primary objectives of this study were to clarify the influence of Radioactive iodine (RAI) on the survival in rare oxyphilic subtype of thyroid cancer (Hürthle Cell Carcinoma, HCC). Methods: Patients diagnosed with oxyphilic thyroid carcinoma from 2004 to 2015 were extracted from the Surveillance, Epidemiology, and End Results Program database. The Kaplan-Meier method was used to compare overall survival (OS) and cancer-specific survival (CSS) among patients who had adjuvant RAI use or not. Univariate and multivariate Cox proportional hazard models were performed for survival analysis, and subsequently visualized by nomogram. Results: In all, 2799 patients were identified, of which 1529 patients had adjuvant RAI use while 1270 patients had not. Based on multivariate Cox analysis, the RAI therapy confers an improved OS for HCC patients (HR = 0.57, 95% CI = 0.44-0.72, P < 0.001), whereas it has no significant benefit in the survival analysis regarding CSS (HR = 0.79, 95% CI = 0.47-1.34, P = 0.382). In a subgroup analysis, the same survival benefit of RAI treatment on OS, but not CSS was observed among patients stratified by AJCC stage and tumor extension. Nevertheless, patients with regional lymph node metastasis benefited from RAI therapy both in OS and CSS (P < 0.001, respectively). Furthermore, nomograms used for predicting long term survival of HCC patients exhibited a better prediction power for OS compared with traditional tumor, nodal and metastatic (TNM) stage made by American Joint Committee on Cancer (AJCC) (Cindex = 0.833 of the nomogram model vs. 0.696 of the AJCC system). Conclusions: This study suggests that RAI therapy is significantly associated with improved OS in patients with Hürthle Cell Carcinoma. However, there were no association between treatment with radioiodine and CSS, possibly due to small number of deaths that were related to HCC.