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. 2025 Nov 5.
doi: 10.1111/cen.70054. Online ahead of print.

Surgical Outcomes Following Neoadjuvant-Targeted Therapy for Advanced Differentiated Thyroid Cancer-Real-World Data

Alexandra Dorman  1   2 , Genady Shendler  2   3 , Anton Warshavsky  1   2 , Nidal Muhanna  1   2 , Gilad Horowitz  1   2 , Liyona Kampel Furman  1   2 , Shahaf Shilo  1   2 , Ben-Zion Joshua  4   5 , Eran Alon  2   6 , Eric Remer  2   6 , Galit Avior  2   6 , Avi Khafif  7 , Orit Gutfeld  2   8 , Elena Izkhakov  2   9 , Jobran Mansour  10 , Inbar Finkel  2   11
Affiliations

Surgical Outcomes Following Neoadjuvant-Targeted Therapy for Advanced Differentiated Thyroid Cancer-Real-World Data

Alexandra Dorman et al. Clin Endocrinol (Oxf). .

Abstract

Background: Differentiated thyroid carcinoma (DTC) is typically managed surgically with favourable outcomes. However, surgery may have dire consequences when the tumour invades critical structures. Neoadjuvant therapy with tyrosine kinase inhibitors (TKIs) has emerged as a potential strategy to improve resectability and reduce morbidity in advanced DTC. We evaluated the efficacy and safety of neoadjuvant TKI therapy in patients with advanced or unresectable DTC.

Methods: A retrospective study was conducted on patients with advanced DTC treated with neoadjuvant TKIs (lenvatinib or dabrafenib/trametinib) followed by curative intent surgery between 2023 and 2025. Data on disease extent, genetic alterations, treatment regimens, and adverse effects were collected. Radiologic response was assessed by CT or PET-CT according to the RECIST 1.1 criteria. Surgical outcomes were evaluated by the degree of morbidity and by tumour involvement in the surgical margins.

Results: Nine patients were included, seven treated with lenvatinib, two treated with dabrafenib/trametinib on the basis of molecular alterations. The median duration of TKI therapy was 5 months, and no disease progression was observed throughout. Radiological assessment revealed a median reduction in tumour burden of 23.53%, contributing to improved tumour resectability. All patients underwent surgical resection with preservation of critical structures. Elevated TSH levels during neoadjuvant therapy was correlated with a positive treatment response (p = 0.028).

Conclusions: Neoadjuvant TKIs may improve the surgical outcomes of patients with advanced DTC. Decision-guided radiological and blood-based surrogate biomarkers, such as TSH, can assist in evaluating treatment response and guide decisions regarding treatment duration and extent of surgical resection.

Keywords: TKIs; neoadjuvant therapy; organ preservation; thyroid neoplasms; tumour resectability.

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