Augmentation of Radioiodine Uptake by Pulmonary Metastasis of Papillary Thyroid Carcinoma Treated with Dabrafenib and Trametinib

Abstract

Redifferentiation therapy with Dabrafenib (a BRAF inhibitor) and Trametinib (a MEK inhibitor) restores radioiodine avidity of radioiodine-refractory papillary thyroid carcinoma (PTC). A 50-year-old man was diagnosed with radioiodine-refractory PTC pulmonary metastasis post prior total thyroidectomy and radioiodine ablation. The patient was treated with Dabrafenib and Trametinib, followed by second radioiodine ablation with I-131 sodium iodine. Diffuse increased radioiodine uptake by pulmonary metastasis was visualized on post ablation whole body scan. Response to second radioiodine ablation was demonstrated by decrease in size of pulmonary nodules seen on chest CT, along with decrease of thyroglobulin level.

Fig. 1 Whole body radioiodine scintigraphy imaging of pulmonary metastasis of papillary thyroid carcinoma. A 50-year-old man was diagnosed with papillary thyroid carcinoma (PTC) with lymph node metastasis and tested positive for BRAF-V600E mutation. The patient underwent total thyroidectomy with bilateral and central lateral neck dissection, followed by first radioiodine ablation with 4.662 GBq (126 mCi) of I-131 sodium iodide at 2 months after thyroidectomy. Subsequently, the patient was diagnosed with a 6 cm cervical nodal metastasis lesion and numerous pulmonary nodules at 6 months post first radioiodine ablation. After surgical removal of cervical nodal mass, the patient was treated with Dabrafenib at a dose of 150 mg × 2/day and Trametinib at a dose of 2 mg/day for 4 months, followed by second radioiodine ablation. a. Whole body post ablation scan revealed no radioiodine avid distant metastasis of papillary thyroid carcinoma in a patient received first radioiodine ablation with 4.662 GBq (126 mCi) of I-131 sodium iodide at 2 months after total thyroidectomy. b. Diagnostic whole body radioiodine scan demonstrated radioiodine uptake by left supraclavicular node and pulmonary nodules in the bilateral lungs treated with Dabrafenib and Trametinib after oral administration of 0.1665 GBq (4.5 mCi) of I-123 sodium iodide. c. Whole body post ablation scan demonstrated diffuse increased radioiodine uptake by the pulmonary metastasis in bilateral lungs treated with Dabrafenib and Trametinib after radioiodine ablation with oral administration of 7.474 GBq (202 mCi) of I-131 sodium iodide

Fig. 2 Decrease in size of pulmonary nodules by CT chest. a. Several 2 to 3 mm pulmonary nodules in bilateral lungs on CT chest obtained 3 months after first radioiodine ablation with 4.662 GBq (126 mCi) of I-131 sodium iodide. b. Interval increase in size of pulmonary nodules in bilateral lungs and pulmonary metastasis of papillary thyroid carcinoma was proven by biopsy of lung nodules. c. Interval decrease in size of pulmonary nodules by CT chest at 3 months post second radioiodine ablation with 7.474 GBq (202 mCi) of I-131 sodium iodide, after treatment of the patient with Dabrafenib and Trametinib prior to second radioiodine ablation. In addition to interval decrease in size of pulmonary nodules, therapeutic effects of second radioiodine ablation post redifferentiation therapy with Dabrafenib and Trametinib were also demonstrated by decrease of thyroglobulin level (14 ng/mL post thyroidectomy and prior to first radioiodine ablation, 93 ng/mL at 6 months post first radioiodine ablation, and 30 ng/mL post second radioiodine ablation). Redifferentiation of radioiodine-refractory PTC after treatment with Dabrafenib and Trametinib could restore radioiodine avidity of radioiodine-refractory PTC for effective radioiodine ablation of radioiodine-refractory PTC [1–4]. The findings from current study demonstrated that combined redifferentiation with Dabrafenib and Trametinib and subsequent radioiodine ablation were effective for treatment of pulmonary metastasis of radioiodine-refractory PTC

Authors' contributions

Fangyu Peng participated in the study conception, drafting of the manuscript, data acquisition and analysis, manuscript revision, and approval of the final content of the manuscript. Elona Malja and Asha Kandathil participated in data acquisition and data analysis, manuscript revision, and approval of the final content of the manuscript. All authors read and approved the final manuscript.

Data Availability

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

Declarations

Conflict of Interest

Elona Malja, Asha Kandathil, and Fangyu Peng declare that they have no conflict of interest. There is no source of funding.

Ethical Approval

All procedures performed in study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Consent to Participate

The institutional review board of our institute approved this retrospective study, and the requirement to obtain informed consent was waived.

Consent for Publication

The institutional review board at our institution approved this retrospective study, and the requirement to obtain informed consent was waived.