英国伦敦大学学院癌症研究所Allan Hackshaw团队研究了英国低风险分化型甲状腺癌症患者术后使用或不使用放射性碘的甲状腺切除术对预后的影响。该项研究成果发表在2025年6月18日出版的《柳叶刀》上。

分化型甲状腺癌患者常在甲状腺全切除术后行术后放射性碘（也称放射性碘消融）治疗。IoN试验旨在评估低风险分化型甲状腺癌患者在无消融与消融后的无复发生存率是否差别不大。

IoN是一项多中心、非劣效性、3期随机试验，在33个英国癌症中心进行。符合条件的患者在甲状腺全切除术后进行了完全切除（R0）；即pT1、pT2、pT3期（根据肿瘤、淋巴结、转移分期版本7 [TNM7]）或pT3a期（根据TNM8）疾病；以及N0、Nx或N1a疾病。参与者通过最小化（1:1）随机分配，使用中央电子系统，在甲状腺切除术后进行1.1 GBq消融或不消融。分层因素为中心、年龄、T分期和淋巴结状态。患者每年进行颈部超声扫描和6个月进行血清甲状腺球蛋白检测。主要终点是5年无复发生存期，定义为无局部复发或持续性结构性疾病、远处转移或甲状腺癌死亡。非劣效性评估的幅度为5个百分点。对主要终点进行了方案和意向治疗（ITT）分析，并对方案人群进行了安全性分析。

2012年6月26日至2020年3月18日，研究人员招募了504例患者（其中女性390例[77%]，男性114例[23%]），随机分配251例不接受消融治疗，253例接受消融治疗（ITT人群）。无消融术组249例患者未行消融术，消融术组231例患者行消融术（按方案人群）。无消融组的中位随访时间为6.8年（IQR为5.6 - 8.6），消融组的中位随访时间为6.6年（IQR为4.8 - 8.5）；17例复发(未消融组8例，消融组9例；ITT人群)在随访期间发生。ITT分析中，无消融组的5年无复发率为97.9% (95% CI为96.1 ~ 99.7)，消融组为96.3%(95.9 ~ 98.7)；按方案分析中，无消融组为97.9%(96.1 ~ 99.7)，无消融组为96.9%（94.7 ~ 99.1）。5年绝对风险差异为0.5个百分点(95% CI -2 ~ 3.2， pnon-劣效性= 0.033；ITT分析)，表明达到非劣效性。

研究组观察到pT3或pT3a肿瘤患者的复发率较高（46例pT3或pT3a肿瘤患者中有4例[9%]，458例pT1或pT2肿瘤患者中有13例[3%]），或N1a肿瘤（47例N1a患者中有6例[13%]，457例N0或Nx患者中有11例[2%]），但未接受消融术的患者的复发率相似。两组之间的不良事件相似，最常见的是疲劳（无消融组249例中有63例[25%]对消融组231例中有65例[28%]）、嗜睡（34例[14%]对32例[14%]）和口干（24例[10%]对21例[9%]），无治疗相关死亡。

综上，离子试验表明，pT1、pT2、N0或Nx肿瘤患者无不良特征，可避免消融（或术后放射性碘）。全世界许多低风险分化甲状腺癌患者可以安全地避免术后放射性碘及其相关的住院治疗和副作用，从而降低医疗保健费用。

附：英文原文

Title: Thyroidectomy with or without postoperative radioiodine for patients with low-risk differentiated thyroid cancer in the UK (IoN): a randomised, multicentre, non-inferiority trial

Author: Ujjal Mallick, Kate Newbold, Matthew Beasley, Kate Garcez, Jonathan Wadsley, Sarah J Johnson, Tim Stephenson, Mark Gaze, Andrew Goodman, Sarah Jefferies, Suganya Sivabalasingham, Nicholas Slevin, David P Wilkinson, Elena Macias-Fernandez, Danielle Power, Tom Roques, Lesley Speed, Christopher Nutting, George Mochloulis, Georgina Gerrard, Charles Candish, Sally Morgan, Devashish Tripathi, Peter Truran, Claire Arthur, Andrzej Wieczorek, Krishnaswamy Madhavan, Jillian Maclean, David Boote, Dae Kim, Abigail Pascoe, Gayani Pitiyage, Sharon Forsyth, Emily Ambrose, Elizabeth Chang, Kate Farnell, Allan Hackshaw

Issue&Volume: 2025-06-18

Abstract:

Background

Patients with differentiated thyroid cancer can often be treated with postoperative radioiodine (also called radioiodine ablation) after total thyroidectomy. The IoN trial was designed to assess whether recurrence-free survival was non-inferior after no ablation compared with ablation in patients with low-risk differentiated thyroid cancer.

Methods

IoN was a multicentre, non-inferiority, phase 3 randomised trial conducted at 33 UK cancer centres. Eligible patients had complete (R0) resection following total thyroidectomy; stage pT1, pT2, pT3 (according to Tumour, Node, Metastasis staging version 7 [TNM7]), or pT3a (according to TNM8) disease; and N0, Nx, or N1a disease. Participants were randomly assigned (1:1) by minimisation, using a central electronic system, to have either 1·1 GBq ablation or no ablation, following thyroidectomy. Stratification factors were centre, age, T stage, and nodal status. Patients had annual neck ultrasound scans and 6-monthly serum thyroglobulin measurements. The primary endpoint was 5-year recurrence-free survival, defined by the absence of locoregional recurrent or persistent structural disease, distant metastases, or death from thyroid cancer. Non-inferiority was assessed with a margin of 5 percentage points. Per-protocol and intention-to-treat (ITT) analyses were done for the primary endpoint, and safety was analysed in the per-protocol population. The trial is registered with ClinicalTrials.gov (NCT01398085), ISRCTN (ISRCTN80416929), and EUDRACT (2011–000144–21), and is still in active follow-up.

Findings

We recruited 504 patients (including 390 [77%] female patients and 114 [23%] male patients) between June 26, 2012 and March 18, 2020 and randomly assigned 251 to receive no ablation and 253 to receive ablation (ITT population). 249 patients in the no ablation group did not have ablation and 231 in the ablation group had ablation (per-protocol population). Median follow-up was 6·8 years (IQR 5·6–8·6) in the no ablation group and 6·6 years (4·8–8·5) in the ablation group; 17 recurrences (eight in the no ablation group and nine in the ablation group; ITT population) occurred during follow-up. 5-year recurrence-free rates were 97·9% (95% CI 96·1–99·7) in the no ablation group versus 96·3% (93·9–98·7) in the ablation group in the ITT analysis, and 97·9% (96·1–99·7) versus 96·9% (94·7–99·1) in the per-protocol analysis. The 5-year absolute risk difference was 0·5 percentage points (95% CI –2·2 to 3·2, pnon-inferiority=0·033; ITT analysis), showing that non-inferiority was reached. The observed recurrence rate was higher among patients with pT3 or pT3a tumours (four [9%] of 46 patients overall with pT3 or pT3a tumours vs 13 [3%] of 458 with pT1 or pT2 tumours), or N1a tumours (six [13%] of 47 with N1a vs 11 [2%] of 457 with N0 or Nx), but they were similar among those who did not receive ablation. Adverse events were similar between the groups, the most common being fatigue (63 [25%] of 249 in the no ablation group vs 65 [28%] of 231 in the ablation group), lethargy (34 [14%] vs 32 [14%]), and dry mouth (24 [10%] vs 21 [9%]), and there were no treatment-related deaths.

Interpretation

The IoN trial shows that ablation (or postoperative radioiodine) can be avoided for patients with pT1, pT2, and N0 or Nx tumours with no adverse features. Many patients with low-risk differentiated thyroid cancer worldwide can safely avoid postoperative radioiodine and its related hospitalisation and side-effects, which in turn results in lower health-care costs.

DOI: 10.1016/S0140-6736(25)00629-4

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)00629-4/abstract