IoN Trial – Is Ablative Radioiodine Necessary? – Rodrigo Arrangoiz MS, MD, FACS, FSSO

Name: IoN – Is Ablative Radioiodine Necessary?
Type:
- Multicenter, open-label, non-inferiority RCT across 33 UK cancer centers
Enrollment Period:
- June 2012 to March 2020
Participants:
- 504 patients post–total thyroidectomy:
  - R0 resection
Pathology Stage:
- pT1 to pT3 (TNM 7 edition):
  - Including pT3a (TNM 8 edition)
- Nodes:
  - N0, Nx, or N1a
- Exclusions:
  - pT1a unifocal
  - pN1b
  - M1
  - Aggressive variants
Intervention and Follow-Up:
- Randomization (1:1):
  - RAI Arm:
    - 1.1 GBq (30 mCi) RAI post-surgery
  - No RAI Arm:
    - Surveillance only
- Preparation:
  - rhTSH used where standard:
    - All received TSH suppression
- Monitoring:
  - Neck US annually
  - Thyroglobulin (Tg) every 6 months
- Primary Endpoint:
  - 5-year recurrence-free survival (RFS):
    - Absence of locoregional or distant structural disease or thyroid cancer related death
- Statistical Non-Inferiority Margin:
  - 5% absolute difference
Stratified Outcomes and Safety:
- Subgroup analysis:
  - Recurrence was slightly higher for:
    - pT3 / pT3a tumors (9%) vs pT1 to pT2 (3%)
    - N1a nodes had 13% recurrence versus 2% in N0 / Nx
  - Adverse events:
    - Similar between arms
    - Most common were:
      - Fatigue (~ 25%),
      - Lethargy (~ 14%)
      - Dry mouth (~ 10%)
      - No treatment-related deaths
Clinical Implications for Head and Neck Surgeons:
- RAI omission is safe in patients meeting strict criteria (pT1 to pT2, N0 / Nx, complete thyroidectomy):
  - With no compromise in 5-year RFS
- Non-inferiority achieved:
  - Difference lies well within prespecified 5% margin
- Patient-centered benefits:
  - Avoids radiation isolation
  - Reduces side effects
  - Enhances QoL:
    - Especially important for younger patients
- RAI may still be considered for pT3 / pT3a or N1a cases:
  - Due to higher recurrence observed:
    - Individual multidisciplinary tumor board (MDT) discussion is warranted
- Supports 2025 Lancet recommendations:
  - Omission of adjuvant RAI is reasonable in selected low-risk DTC patients
Final Take-Home Points:
- IoN validates RAI omission in strictly defined low-risk DTC post-total thyroidectomy:
  - 98% RFS at 5 years without RAI
- Reinforces a move toward risk-adapted, de-escalated care in line with ATA risk guidelines and emerging global consensus
- Tailor decision-making in MDT:
  - Offer RAI to > T2 or with nodal involvement:
    - Otherwise, provide informed reassurance and structured surveillance