Genotype-Driven Neoadjuvant Therapy for Locally Advanced Thyroid Cancer: A Real-World Cohort Study

Summary

This multicenter registry tests whether genomically matched neoadjuvant therapy (1-4 cycles tailored to BRAF V600E, RET fusion/mutation, isolated TERT mutation, triple-negative BRAF/RET/TERT, or ICI ± TKI) can render locally advanced, initially unresectable-or high-morbidity-thyroid cancers operable. The primary endpoint is conversion-to-surgery; key secondaries are R0/1 margin rate and 12-month event-free survival, with propensity-score weighting correcting cohort imbalances. Findings aim to define a precision-guided neoadjuvant standard for down-staging advanced thyroid tumors.

Conditions

• Thyroid Neoplasms

Interventions

DRUG

Dabrafenib

150 mg orally twice daily; ≤4 × 28-day cycles

DRUG

Trametinib

2 mg orally once daily; same duration

DRUG

Selpercatinib

160 mg orally twice daily; ≤4 cycles

DRUG

Pralsetinib

retrospective, 400 mg orally once daily; ≤4 cycles

DRUG

Lenvatinib

24 mg orally once daily; ≤4 cycles

DRUG

Larotrectinib

Larotrectinib 100 mg orally twice daily, continuous 28-day cycles.

DRUG

Anlotinib

12 mg orally once daily; 2 weeks on / 1 week off, ≤4 cycles (alternative)

DRUG

Pembrolizumab

200 mg IV infusion every 3 weeks; ≤4 cycles

DRUG

Sintilimab

200 mg IV infusion every 3 weeks; ≤4 cycles

DRUG

Cabozantinib

Cabozantinib 60 mg orally once daily, continuous 28-day cycles.

DRUG

Bemosuzumab

China PD-L1 antibody bemosuzumab 900 mg IV every 2 weeks (14-day cycle).

PROCEDURE

Conversion Surgery

Conversion Surgery if resectable

Sponsors & Collaborators

• Fujian Medical University

  lead OTHER

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-07-01

Primary Completion

2027-12-31

Completion

2028-12-31

Countries

• China

Study Locations