Adjuvant External Beam Radiotherapy Reduces Local Recurrence in Poorly Differentiated Thyroid Cancer : A Multicenter Retrospective Cohort Study Describing Outcomes in the Treatment of Resectable Poorly Differentiated Thyroid Cancer

Pascal K C Jonker; Jan H Koetje; John Turchini; Jia Feng Alex Lin; Anthony J Gill; Thomas Eade; Ahmad Aniss; Roderick Clifton-Bligh; Bettien M van Hemel; Diana Learoyd; Hans H G Verbeek; Thera P Links; Bruce Robinson; Venessa Tsang; Stanley Sidhu; Schelto Kruijff; Mark S Sywak

doi:10.1245/s10434-025-17434-2

Adjuvant External Beam Radiotherapy Reduces Local Recurrence in Poorly Differentiated Thyroid Cancer : A Multicenter Retrospective Cohort Study Describing Outcomes in the Treatment of Resectable Poorly Differentiated Thyroid Cancer

Ann Surg Oncol. 2025 May 23. doi: 10.1245/s10434-025-17434-2. Online ahead of print.

Authors

Pascal K C Jonker^{1

2}, Jan H Koetje², John Turchini^{3

4

5}, Jia Feng Alex Lin^{1

2}, Anthony J Gill^{3

6

7}, Thomas Eade⁸, Ahmad Aniss¹, Roderick Clifton-Bligh^{3

9}, Bettien M van Hemel¹⁰, Diana Learoyd^{3

9}, Hans H G Verbeek¹¹, Thera P Links¹², Bruce Robinson^{3

9}, Venessa Tsang^{3

9}, Stanley Sidhu^{1

3}, Schelto Kruijff², Mark S Sywak^{13

14}

Affiliations

¹ University of Sydney Endocrine Surgical Unit, Royal North Shore Hospital, Northern Sydney Local Health District, St. Leonards, Australia.
² Department of Surgery, Division of Surgical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
³ Northern Clinical School, Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
⁴ Douglass Hanly Moir Pathology, Macquarie Park, NSW, Australia.
⁵ Discipline of Pathology, MQ Health, Macquarie University, Macquarie Park, NSW, Australia.
⁶ Department of Anatomical Pathology, NSW Health Pathology, Royal North Shore Hospital, Northern Sydney Local Health District, St. Leonards, NSW, Australia.
⁷ Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW, Australia.
⁸ Department of Radiation Oncology, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW, Australia.
⁹ Department of Endocrinology, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, Australia.
¹⁰ Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
¹¹ Department of Radiotherapy, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
¹² Department of Internal Medicine, Division of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
¹³ University of Sydney Endocrine Surgical Unit, Royal North Shore Hospital, Northern Sydney Local Health District, St. Leonards, Australia. marksywak@nebsc.com.au.
¹⁴ Northern Clinical School, Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia. marksywak@nebsc.com.au.

PMID: 40408021
DOI: 10.1245/s10434-025-17434-2

Abstract

Background: Poorly differentiated thyroid carcinoma (PDTC) accounts for 5% of all thyroid cancers and is responsible for a large proportion of thyroid cancer-related deaths. The optimal treatment approach is not clear. This study aimed to evaluate the effect of postoperative intensity-modulated radiotherapy (IMRT) on the treatment of resectable PDTC. Additionally, treatment-related morbidity, characteristics of ¹³¹I-refractory disease, and factors affecting survival were assessed.

Methods: The study included consecutive PDTC cases from 1997 to 2018, defined according to Turin criteria and treated in two tertiary referral centers. Surgery, IMRT, ¹³¹I, and systemic therapies were administered based on multidisciplinary team recommendations. The primary study outcome was 5-year local control after IMRT in cases with positive resection margins (micro- and macroscopic). The secondary outcomes were treatment-related morbidity within 30-days after completion of treatment (Clavien-Dindo and Common Terminology Criteria for Adverse Events [CTC-AE] 5.0), ¹³¹I-refractory disease characteristics using standardized definitions, and factors influencing survival.

Results: Among 51 PDTC cases, 53% presented with metastatic disease. Adjuvant IMRT improved 5-year local control (100% vs. 17.5%; p = 0.02), with a higher number of grades 1 to 3 complications (p = 0.005) versus cases without IMRT. Within 13 months, ¹³¹I-refractory disease occurred in 62.7% of the patients and was more common in non-survivors (86.6% vs. 52.8%; p = 0.01). Positive resection margins and extrathyroidal extension were associated with poor survival in the univariate analysis, but were not significant in the multiple regression analysis.

Conclusion: Adjuvant IMRT may reduce thyroid bed recurrence in resectable PDTC with positive resection margins, but is associated with increased treatment-related complications. ¹³¹I-refractory disease occurs frequently, with non-survivors progressing earlier to ¹³¹I resistance.

Keywords: 131I-refractory; Cancer; PDTC; Poorly differentiated; Radiotherapy; Surgery; Thyroid; Turin.