Pathologic and radiologic response to neoadjuvant therapy in advanced differentiated thyroid cancer

Area of Science:

• Oncology
• Pathology
• Surgical Oncology

Background:

• Locally advanced differentiated thyroid cancer (DTC) often requires neoadjuvant therapy to reduce tumor size before surgery.
• Histopathologic changes from neoadjuvant treatments can guide surgical planning and optimize treatment protocols for better outcomes.

Purpose of the Study:

• To analyze the histopathologic effects of neoadjuvant therapies in locally advanced DTC.
• To correlate these changes with radiologic response and surgical outcomes.

Main Methods:

• Retrospective analysis of 9 patients with unresectable, locally advanced DTC treated with lenvatinib or dabrafenib/trametinib.
• Histopathologic evaluation of resection specimens using H&E and IHC for CD3, CD31, ERG.
• Assessment of tumor fibrosis, necrosis, vascularity, and immune infiltration.

Main Results:

• All patients achieved tumor regression enabling surgical resection.
• Lenvatinib induced significant vascular remodeling, reduced microvessel density, and increased lymphocytic infiltration.
• BRAF-targeted therapy (dabrafenib/trametinib) primarily caused tumor fibrosis with minimal vascular or immune changes.
• Neoadjuvant therapy was well-tolerated, without increased surgical morbidity.

Conclusions:

• Neoadjuvant therapy facilitates complete (R0) resection in locally advanced DTC.
• Distinct histopathologic responses to lenvatinib (vascular/immune) versus dabrafenib/trametinib (fibrosis) may inform future treatment strategies.