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Background <p>Radioiodine-refractory (RAIR) differentiated thyroid carcinoma (DTC), particularly those harboring <i>BRAF V600E</i> mutations, is associated with poor prognosis due to loss of iodine avidity. Pharmacologic MAPK pathway inhibition with <i>BRAF</i> inhibitors has emerged as a potential redifferentiation strategy to restore iodine uptake and enable further radioiodine (RAI) therapy.</p> Objective <p>To describe clinical and imaging outcomes of redifferentiation therapy with short-term dabrafenib in patients with metastatic <i>BRAF V600E</i>–mutant papillary thyroid carcinoma (PTC).</p> Methods <p>We retrospectively analyzed four consecutive patients with metastatic <i>BRAF V600E</i>–positive PTC and disease refractory to prior RAI therapy. All patients received dabrafenib 150&#xa0;mg twice daily for 30 days, followed by RAI (100 mCi I-131) under TSH stimulation either by hormone withdrawal or recombinant human TSH. Pre- and post-treatment imaging and biochemical markers were assessed to evaluate iodine uptake and treatment response.</p> Results <p>Three of the four patients exhibited new or increased iodine uptake in metastatic lung or nodal sites after dabrafenib therapy. Structural or biochemical responses were observed in two patients: one showed partial response and TgAb decline; the other achieved disease stabilization with biochemical stability. One of these patients, who had previously achieved a complete response after lenvatinib but developed severe adverse events, successfully underwent redifferentiation with stabilization of disease. In contrast, one patient showed no iodine uptake or response. No significant toxicities related to dabrafenib were reported.</p> Conclusion <p>Short-term BRAF inhibition with dabrafenib enabled redifferentiation and restored RAI avidity in a subset of patients with <i>BRAF V600E</i>–mutant metastatic PTC, with clinical benefit. This approach may be particularly useful in patients ineligible for multikinase inhibitors or as a bridge to re-treatment with I-131. Further prospective studies are warranted to identify predictors of response and to optimize timing, duration, and sequencing of redifferentiation strategies.</p>

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Short-Term BRAF Inhibition with Dabrafenib induced redifferentiation in a subset of patients with BRAF V600E–Mutant papillary thyroid carcinoma

  • 期刊论文

  • 发表日期：

    2025年12月29日

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  • Fabián Pitoia,
  • Fernando Jerkovich,
  • Martina Rodrigo,
  • Nahiara Woniatczuk,
  • Erika Abelleira

摘要

Background

Radioiodine-refractory (RAIR) differentiated thyroid carcinoma (DTC), particularly those harboring BRAF V600E mutations, is associated with poor prognosis due to loss of iodine avidity. Pharmacologic MAPK pathway inhibition with BRAF inhibitors has emerged as a potential redifferentiation strategy to restore iodine uptake and enable further radioiodine (RAI) therapy.

Objective

To describe clinical and imaging outcomes of redifferentiation therapy with short-term dabrafenib in patients with metastatic BRAF V600E–mutant papillary thyroid carcinoma (PTC).

Methods

We retrospectively analyzed four consecutive patients with metastatic BRAF V600E–positive PTC and disease refractory to prior RAI therapy. All patients received dabrafenib 150 mg twice daily for 30 days, followed by RAI (100 mCi I-131) under TSH stimulation either by hormone withdrawal or recombinant human TSH. Pre- and post-treatment imaging and biochemical markers were assessed to evaluate iodine uptake and treatment response.

Results

Three of the four patients exhibited new or increased iodine uptake in metastatic lung or nodal sites after dabrafenib therapy. Structural or biochemical responses were observed in two patients: one showed partial response and TgAb decline; the other achieved disease stabilization with biochemical stability. One of these patients, who had previously achieved a complete response after lenvatinib but developed severe adverse events, successfully underwent redifferentiation with stabilization of disease. In contrast, one patient showed no iodine uptake or response. No significant toxicities related to dabrafenib were reported.

Conclusion

Short-term BRAF inhibition with dabrafenib enabled redifferentiation and restored RAI avidity in a subset of patients with BRAF V600E–mutant metastatic PTC, with clinical benefit. This approach may be particularly useful in patients ineligible for multikinase inhibitors or as a bridge to re-treatment with I-131. Further prospective studies are warranted to identify predictors of response and to optimize timing, duration, and sequencing of redifferentiation strategies.